{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://erepo.genome.network/evrepo/api/summary/classification/dcf417cb-44a7-42fd-ac34-f899ff29d765/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1528074022", "label": "ClinGen Thrombosis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for SERPINC1 Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0013144", "id": "MONDO:0013144", "label": "antithrombin III deficiency", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343772824/MONDO:0013144/084/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343772824/MONDO:0013144/084/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50064_EP169601587241724", "id": "CG-PCER-AGENT:CG_50064_EP169601587241724", "type": "Agent" }, "contributionDate": { "date": "2024/12/20", "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/CA343772824/MONDO:0013144/084/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA343772824/MONDO:0013144/084/ci/CA343772824/MONDO:0013144/084.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50064_EP169601587241724", "id": "CG-PCER-AGENT:CG_50064_EP169601587241724", "type": "Agent" }, "comments": "The highest population minor allele frequency in gnomAD v4.1 is 0.000001 (2/1179816 alleles) in European non-Finnish population, which is lower than the ClinGen Thrombosis VCEP threshold (<0.00002) for PM2_Supporting, meeting this criterion (PM2_Supporting).", "contributionDate": { "date": "2024/12/20", "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": "CA343772824/MONDO:0013144/084/ci/CA343772824/MONDO:0013144/084.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA343772824/MONDO:0013144/084/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA343772824/MONDO:0013144/084/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA343772824/MONDO:0013144/084/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343772824/MONDO:0013144/084/el/0/1699", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343772824/MONDO:0013144/084/ei/1/1700", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50064_EP169601587241724", "id": "CG-PCER-AGENT:CG_50064_EP169601587241724", "type": "Agent" }, "contributionDate": { "date": "2024/12/20", "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/CA343772824/MONDO:0013144/084/el/0/1699/1701", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA343772824/MONDO:0013144/084/ci/CA343772824/MONDO:0013144/084.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50064_EP169601587241724", "id": "CG-PCER-AGENT:CG_50064_EP169601587241724", "type": "Agent" }, "comments": "This variant has been reported in at least four more probands meeting an antithrombin activity level of < 0.8 IU/mL; due to the absence of specified repeat testing, crossed electrophoresis showing abnormal results and family members with reported antithrombin activity levels below the threshold three of these probands were scored at only half a point. (2.5 points) (PS4_Moderate; PMIDs:34207366, 8217824, 31030036, 23932013).", "contributionDate": { "date": "2024/12/20", "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": "CA343772824/MONDO:0013144/084/ci/CA343772824/MONDO:0013144/084.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA343772824/MONDO:0013144/084/0/1699/1701", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA343772824/MONDO:0013144/084/1/1700", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA343772824/MONDO:0013144/084/0/1699", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343772824/MONDO:0013144/084/el/0/1762", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343772824/MONDO:0013144/084/ei/1/1763", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50064_EP169601587241724", "id": "CG-PCER-AGENT:CG_50064_EP169601587241724", "type": "Agent" }, "contributionDate": { "date": "2024/12/20", "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/CA343772824/MONDO:0013144/084/el/0/1762/1764", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA343772824/MONDO:0013144/084/ci/CA343772824/MONDO:0013144/084.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50064_EP169601587241724", "id": "CG-PCER-AGENT:CG_50064_EP169601587241724", "type": "Agent" }, "comments": "The c.1171C>T (p.Arg391Ter) variant in SERPINC1 is a nonsense variant that may cause loss of function of the protein, however it is predicted to escape nonsense mediated decay and remove >10% of the protein (PVS1_Strong).", "contributionDate": { "date": "2024/12/20", "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": "CA343772824/MONDO:0013144/084/ci/CA343772824/MONDO:0013144/084.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA343772824/MONDO:0013144/084/0/1762/1764", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA343772824/MONDO:0013144/084/1/1763", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA343772824/MONDO:0013144/084/0/1762", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343772824/MONDO:0013144/084/el/0/1648", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343772824/MONDO:0013144/084/ei/1/1649", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50064_EP169601587241724", "id": "CG-PCER-AGENT:CG_50064_EP169601587241724", "type": "Agent" }, "contributionDate": { "date": "2024/12/20", "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/CA343772824/MONDO:0013144/084/el/0/1648/1650", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA343772824/MONDO:0013144/084/ci/CA343772824/MONDO:0013144/084.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50064_EP169601587241724", "id": "CG-PCER-AGENT:CG_50064_EP169601587241724", "type": "Agent" }, "comments": "The variant has been reported to segregate with autosomal dominant hereditary antithrombin deficiency in 15 affected family members from two families (PP1_Strong; PMIDs:34207366, 23932013).", "contributionDate": { "date": "2024/12/20", "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": "CA343772824/MONDO:0013144/084/ci/CA343772824/MONDO:0013144/084.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA343772824/MONDO:0013144/084/0/1648/1650", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA343772824/MONDO:0013144/084/1/1649", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA343772824/MONDO:0013144/084/0/1648", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343772824/MONDO:0013144/084/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343772824/MONDO:0013144/084/ei/1/1634", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50064_EP169601587241724", "id": "CG-PCER-AGENT:CG_50064_EP169601587241724", "type": "Agent" }, "contributionDate": { "date": "2024/12/20", "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/CA343772824/MONDO:0013144/084/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA343772824/MONDO:0013144/084/ci/CA343772824/MONDO:0013144/084.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50064_EP169601587241724", "id": "CG-PCER-AGENT:CG_50064_EP169601587241724", "type": "Agent" }, "comments": "At least one patient with this variant displayed an antithrombin activity level of < 0.8 IU/mL on repeated independent studies, which is highly specific for hereditary antithrombin deficiency (PP4, PMID:29153735).", "contributionDate": { "date": "2024/12/20", "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": "CA343772824/MONDO:0013144/084/ci/CA343772824/MONDO:0013144/084.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA343772824/MONDO:0013144/084/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA343772824/MONDO:0013144/084/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA343772824/MONDO:0013144/084/0/1633", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA343772824/MONDO:0013144/084", "metadata": { "created": "2024-12-20T22:57:22.876Z", "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, 20 Dec 2024 22:57:22 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA6668-3", "id": "LN:LA6668-3", "label": "Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "dcf417cb-44a7-42fd-ac34-f899ff29d765", "variant": { "@id": "https://reg.genome.network/allele/CA343772824", "id": "CAR:CA343772824", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000488.4:c.1171C>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000488.4(SERPINC1):c.1171C>T (p.Arg391Ter)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-04-05T08:34:22.899Z" } }, "status": { "code": 200, "name": "OK" } }