{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/07236833-88e3-4b3a-9a4d-35a6c2230597/doc/sepio/version/2.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1622722963", "label": "ClinGen Urea Cycle Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for OTC Version 1.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0010703", "id": "MONDO:0010703", "label": "ornithine carbamoyltransferase deficiency", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA090910/MONDO:0010703/156/el/0/1798", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA090910/MONDO:0010703/156/ei/1/1799", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50100_EP177998198620257", "id": "CG-PCER-AGENT:CG_50100_EP177998198620257", "type": "Agent" }, "contributionDate": { "date": "2026/9/15", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0011", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "0011", "label": "PM2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA090910/MONDO:0010703/156/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA090910/MONDO:0010703/156/ci/CA090910/MONDO:0010703/156.002", "contribution": [ { "agent": { "@id": 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"SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA090910/MONDO:0010703/156/0/1798", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA090910/MONDO:0010703/156/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA090910/MONDO:0010703/156/ei/1/1832", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50100_EP177998198620257", "id": "CG-PCER-AGENT:CG_50100_EP177998198620257", "type": "Agent" }, "contributionDate": { "date": "2026/9/15", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0018", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "0018", "label": "PP4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA090910/MONDO:0010703/156/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA090910/MONDO:0010703/156/ci/CA090910/MONDO:0010703/156.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50100_EP177998198620257", "id": "CG-PCER-AGENT:CG_50100_EP177998198620257", "type": "Agent" }, "comments": "One patient with this variant displayed hyperammonemia, urinary orotate, 3% OTC activity which is highly specific for OTC deficiency PP4_Moderate ", "contributionDate": { "date": "2026/9/15", "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": "CA090910/MONDO:0010703/156/ci/CA090910/MONDO:0010703/156.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA090910/MONDO:0010703/156/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA090910/MONDO:0010703/156/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA090910/MONDO:0010703/156/0/1831", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA090910/MONDO:0010703/156/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA090910/MONDO:0010703/156/ei/1/1805", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50100_EP177998198620257", "id": "CG-PCER-AGENT:CG_50100_EP177998198620257", "type": "Agent" }, "contributionDate": { "date": "2026/9/15", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0070", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000328", "id": "SEPIO:0000328", "label": "Benign Strong" }, "id": "0070", "label": "BS1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA090910/MONDO:0010703/156/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA090910/MONDO:0010703/156/ci/CA090910/MONDO:0010703/156.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50100_EP177998198620257", "id": "CG-PCER-AGENT:CG_50100_EP177998198620257", "type": "Agent" }, "comments": "The Grpmax Filtered allele frequency in gnomAD v4.1.0 is 0.00000917, which is lower than the ClinGen UCD VCEP’s threshold for BS1 (>0.002000 (0.2%)).", "contributionDate": { "date": "2026/9/15", "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": "CA090910/MONDO:0010703/156/ci/CA090910/MONDO:0010703/156.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA090910/MONDO:0010703/156/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA090910/MONDO:0010703/156/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA090910/MONDO:0010703/156/0/1804", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA090910/MONDO:0010703/156/el/0/1606", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA090910/MONDO:0010703/156/ei/1/1607", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50100_EP177998198620257", "id": "CG-PCER-AGENT:CG_50100_EP177998198620257", "type": "Agent" }, "contributionDate": { "date": "2026/9/15", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0032", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0032", "label": "PS4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA090910/MONDO:0010703/156/el/0/1606/1608", "evidenceItem": [ { "@id": 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"label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA090910/MONDO:0010703/156/0/1606", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA090910/MONDO:0010703/156/el/0/1825", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA090910/MONDO:0010703/156/ei/1/1826", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50100_EP177998198620257", "id": "CG-PCER-AGENT:CG_50100_EP177998198620257", "type": "Agent" }, "contributionDate": { "date": "2026/9/15", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0039", "defaultStrength": { "@id": 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"2026/9/15", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0060", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0060", "label": "PP1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA090910/MONDO:0010703/156/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA090910/MONDO:0010703/156/ci/CA090910/MONDO:0010703/156.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50100_EP177998198620257", "id": "CG-PCER-AGENT:CG_50100_EP177998198620257", "type": "Agent" }, "comments": "The variant has been reported to segregate with OTC in the mother and sister affected \nPP1_SUPPORTING; PMID:7860066", "contributionDate": { "date": "2026/9/15", "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": "CA090910/MONDO:0010703/156/ci/CA090910/MONDO:0010703/156.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA090910/MONDO:0010703/156/0/1678/1680", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA090910/MONDO:0010703/156/1/1679", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA090910/MONDO:0010703/156/0/1678", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA090910/MONDO:0010703/156/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA090910/MONDO:0010703/156/ei/1/1781", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50100_EP177998198620257", "id": "CG-PCER-AGENT:CG_50100_EP177998198620257", "type": "Agent" }, "contributionDate": { "date": "2026/9/15", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/008", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "008", "label": "PM5", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA090910/MONDO:0010703/156/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA090910/MONDO:0010703/156/ci/CA090910/MONDO:0010703/156.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50100_EP177998198620257", "id": "CG-PCER-AGENT:CG_50100_EP177998198620257", "type": "Agent" }, "comments": "Another missense variant [c.119G>A, p.Arg40His] [ClinVar Variation ID 11014, in the same codon has been classified as pathogenic for OTC deficiency by the ClinGen Urea Cycle Disorders VCEP (PM5).\n", "contributionDate": { "date": "2026/9/15", "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": "CA090910/MONDO:0010703/156/ci/CA090910/MONDO:0010703/156.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA090910/MONDO:0010703/156/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA090910/MONDO:0010703/156/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA090910/MONDO:0010703/156/0/1780", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA090910/MONDO:0010703/156/el/0/1690", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA090910/MONDO:0010703/156/ei/1/1691", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50100_EP177998198620257", "id": "CG-PCER-AGENT:CG_50100_EP177998198620257", "type": "Agent" }, "contributionDate": { "date": "2026/9/15", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0025", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "0025", "label": "PP3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA090910/MONDO:0010703/156/el/0/1690/1692", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA090910/MONDO:0010703/156/ci/CA090910/MONDO:0010703/156.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50100_EP177998198620257", "id": "CG-PCER-AGENT:CG_50100_EP177998198620257", "type": "Agent" }, "comments": "The computational predictor REVEL gives a score of 0.902, which is between 0.773 and 0.932, and Moderate evidence of impact on OTC function (PP3_Moderate).\n", "contributionDate": { "date": "2026/9/15", "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": "CA090910/MONDO:0010703/156/ci/CA090910/MONDO:0010703/156.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA090910/MONDO:0010703/156/0/1690/1692", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA090910/MONDO:0010703/156/1/1691", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA090910/MONDO:0010703/156/0/1690", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA090910/MONDO:0010703/156", "metadata": { "created": "2026-09-15T21:35:22.049Z", "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": "Tue, 15 Sep 2026 21:35:21 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "2.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "07236833-88e3-4b3a-9a4d-35a6c2230597", "variant": { "@id": "https://reg.genome.network/allele/CA090910", "id": "CAR:CA090910", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000531.6:c.118C>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000531.6(OTC):c.118C>T (p.Arg40Cys)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-29T20:09:57.781Z" } }, "status": { "code": 200, "name": "OK" } }