{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/008fde91-e932-4956-901c-e2ad7c8c1e7a/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1552193476", "label": "ClinGen X-linked Inherited Retinal Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RPGR Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0100437", "id": "MONDO:0100437", "label": "RPGR-related retinopathy", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412741594/MONDO:0100437/106/el/0/1774", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412741594/MONDO:0100437/106/ei/1/1775", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/9/8", "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/CA412741594/MONDO:0100437/106/el/0/1774/1776", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA412741594/MONDO:0100437/106/ci/CA412741594/MONDO:0100437/106.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "Another missense variant in the same codon, NM_001034853.2:c.823G>A (p.Gly275Ser), (PMIDs: 17480003, 31456290, 17724181, 16969763, and 8817343) has been classified as pathogenic for RPGR-related retinopathy by the ClinGen X-linked IRD VCEP, while no benign missense variants have been identified in this codon. The present variant has a higher Grantham’s distance (159) than the comparison variant (56), and SpliceAI has been used to confirm that neither variant has a predicted impact on RPGR splicing (PM5_Supporting).", "contributionDate": { "date": "2025/9/8", "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": "CA412741594/MONDO:0100437/106/ci/CA412741594/MONDO:0100437/106.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA412741594/MONDO:0100437/106/0/1774/1776", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412741594/MONDO:0100437/106/1/1775", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA412741594/MONDO:0100437/106/0/1774", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412741594/MONDO:0100437/106/el/0/1753", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412741594/MONDO:0100437/106/ei/1/1754", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/9/8", "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/CA412741594/MONDO:0100437/106/el/0/1753/1755", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA412741594/MONDO:0100437/106/ci/CA412741594/MONDO:0100437/106.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "The computational predictor REVEL gives a score of 0.968, which is above the ClinGen X-linked IRD VCEP threshold of ≥ 0.932 and predicts a damaging effect on RPGR function (PP3_Strong). The splicing impact predictor SpliceAI gives a score of 0.02 for splice acceptor gain, which is below the ClinGen X-linked IRD VCEP recommended threshold of ≥0.2 and does not predict a damaging impact on splicing.", "contributionDate": { "date": "2025/9/8", "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": "CA412741594/MONDO:0100437/106/ci/CA412741594/MONDO:0100437/106.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA412741594/MONDO:0100437/106/0/1753/1755", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412741594/MONDO:0100437/106/1/1754", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA412741594/MONDO:0100437/106/0/1753", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412741594/MONDO:0100437/106/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412741594/MONDO:0100437/106/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/9/8", "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/CA412741594/MONDO:0100437/106/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA412741594/MONDO:0100437/106/ci/CA412741594/MONDO:0100437/106.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "This variant is absent from gnomAD v4.1.0 (PM2_Supporting).", "contributionDate": { "date": "2025/9/8", "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": "CA412741594/MONDO:0100437/106/ci/CA412741594/MONDO:0100437/106.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA412741594/MONDO:0100437/106/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412741594/MONDO:0100437/106/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA412741594/MONDO:0100437/106/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412741594/MONDO:0100437/106/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412741594/MONDO:0100437/106/ei/1/1736", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/9/8", "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/CA412741594/MONDO:0100437/106/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA412741594/MONDO:0100437/106/ci/CA412741594/MONDO:0100437/106.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "This variant has been reported in at least 2 apparently unrelated probands diagnosed with retinitis pigmenosa (PMID: 37217489). However, neither individual meets one of the PS4 requirements of some functional vision impairment in affected males by age 30, or decreased or absent cone and/or rod ERG responses, so PS4_Supporting was not met.", "contributionDate": { "date": "2025/9/8", "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": "CA412741594/MONDO:0100437/106/ci/CA412741594/MONDO:0100437/106.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA412741594/MONDO:0100437/106/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412741594/MONDO:0100437/106/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA412741594/MONDO:0100437/106/0/1735", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA412741594/MONDO:0100437/106", "metadata": { "created": "2025-09-08T00:51:10.992Z", "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": "Mon, 08 Sep 2025 00:51:10 -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": "008fde91-e932-4956-901c-e2ad7c8c1e7a", "variant": { "@id": "https://reg.genome.network/allele/CA412741594", "id": "CAR:CA412741594", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_001034853.2:c.823G>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_001034853.2(RPGR):c.823G>T (p.Gly275Cys)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-06T02:11:56.578Z" } }, "status": { "code": 200, "name": "OK" } }