{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/99de4974-7876-4054-8f80-a4970421a472/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/643243093", "label": "ClinGen Hearing Loss Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for OTOF and MYO15A Version 1", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0010860", "id": "MONDO:0010860", "label": "autosomal recessive nonsyndromic hearing loss 3", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/el/0/1765", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/ei/1/1766", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "contributionDate": { "date": "2025/12/19", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/el/0/1765/1767", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8423973/MONDO:0010860/023/ci/CA8423973/MONDO:0010860/023.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "Same amino acid change reported in a signle patient with congenital severe HL PMID : 26969326 (c.4643C>T - p.Ala1548Thr), associated with another missense of unknown significance (c.5866C>T - p.(Arg1956Trp : rare, well predicted, never reported). These arguments doesn't allow to use PS1", "contributionDate": { "date": "2025/12/19", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA8423973/MONDO:0010860/023/ci/CA8423973/MONDO:0010860/023.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/0/1765/1767", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/1/1766", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/0/1765", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/el/0/1651", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/ei/1/1652", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "contributionDate": { "date": "2025/12/19", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/el/0/1651/1653", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8423973/MONDO:0010860/023/ci/CA8423973/MONDO:0010860/023.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "This variant has been detected in 2 probands with hearing loss. Both were compound heterozygous for the variant and a pathogenic or likely pathogenic variant and were confirmed in trans by family testing), (optional - provide list of variants, PM3 points, PMIDs : 26561413, 33398081). Another patient with congenital profound HL were compound heterozygous for this variant and another rare missense of unknown significance (PMID : 26915297) (PM3_Strong).", "contributionDate": { "date": "2025/12/19", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA8423973/MONDO:0010860/023/ci/CA8423973/MONDO:0010860/023.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/0/1651/1653", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/1/1652", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/0/1651", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/ei/1/1697", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "contributionDate": { "date": "2025/12/19", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8423973/MONDO:0010860/023/ci/CA8423973/MONDO:0010860/023.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "Inner hair cells derived from patient IPSc compound for this variant and another missense showed stereocilia length, electrophysiological and F-actin organization abnormalities. This phenotype has been rescued after CRISPR-Cas9 correction of the c.4642G>A variant, indicating that this variant impacts protein function (PMID: 26915297)(PS3_P).", "contributionDate": { "date": "2025/12/19", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA8423973/MONDO:0010860/023/ci/CA8423973/MONDO:0010860/023.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/0/1696", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/ei/1/1805", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "contributionDate": { "date": "2025/12/19", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8423973/MONDO:0010860/023/ci/CA8423973/MONDO:0010860/023.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "contributionDate": { "date": "2025/12/19", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA8423973/MONDO:0010860/023/ci/CA8423973/MONDO:0010860/023.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/0/1804", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "contributionDate": { "date": "2025/12/19", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8423973/MONDO:0010860/023/ci/CA8423973/MONDO:0010860/023.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "The allele frequency of this variant is 0.005% (76/1180010) of European non-finnish chromosomes by gnomAD v.4, which is lower than the thresholds defined by the ClinGen Hearing Loss Expert Panel for PM2_Supporting, meeting this criterion (PM2_Supporting).", "contributionDate": { "date": "2025/12/19", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA8423973/MONDO:0010860/023/ci/CA8423973/MONDO:0010860/023.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "contributionDate": { "date": "2025/12/19", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8423973/MONDO:0010860/023/ci/CA8423973/MONDO:0010860/023.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "The REVEL computational prediction analysis tool produced a score of 0.884, which is above the threshold necessary to apply PP3 (PP3).", "contributionDate": { "date": "2025/12/19", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA8423973/MONDO:0010860/023/ci/CA8423973/MONDO:0010860/023.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/el/0/1702", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/ei/1/1703", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "contributionDate": { "date": "2025/12/19", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/el/0/1702/1704", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8423973/MONDO:0010860/023/ci/CA8423973/MONDO:0010860/023.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "contributionDate": { "date": "2025/12/19", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA8423973/MONDO:0010860/023/ci/CA8423973/MONDO:0010860/023.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/0/1702/1704", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/1/1703", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/0/1702", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/ei/1/1685", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "contributionDate": { "date": "2025/12/19", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8423973/MONDO:0010860/023/ci/CA8423973/MONDO:0010860/023.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "contributionDate": { "date": "2025/12/19", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA8423973/MONDO:0010860/023/ci/CA8423973/MONDO:0010860/023.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/0/1684", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/el/0/1777", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/ei/1/1778", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "contributionDate": { "date": "2025/12/19", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8423973/MONDO:0010860/023/el/0/1777/1779", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8423973/MONDO:0010860/023/ci/CA8423973/MONDO:0010860/023.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "contributionDate": { "date": "2025/12/19", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA8423973/MONDO:0010860/023/ci/CA8423973/MONDO:0010860/023.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/0/1777/1779", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/1/1778", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023/0/1777", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8423973/MONDO:0010860/023", "metadata": { "created": "2025-12-19T15:41:35.275Z", "note": "DISCLAIMER: While the data/content in this document is approved by ClinGen expert panel(s), the SEPIO schema presented here is an initial prototype and has not been reviewed nor finalized by the ClinGen Data Exchange Modeling Team. We expect it to differ significantly from the final schema.", "producedAtUTC": "Fri, 19 Dec 2025 15:41:35 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "99de4974-7876-4054-8f80-a4970421a472", "variant": { "@id": "https://reg.genome.network/allele/CA8423973", "id": "CAR:CA8423973", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_016239.4:c.4642G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_016239.4(MYO15A):c.4642G>A (p.Ala1548Thr)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-23T14:33:01.681Z" } }, "status": { "code": 200, "name": "OK" } }