{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/48f2aa0e-c95d-486e-a0b6-f29bce515120/doc/sepio/version/2.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/643243096", "label": "ClinGen Cerebral Creatine Deficiency Syndromes Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for GAMT Version 2.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "2.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0012999", "id": "MONDO:0012999", "label": "guanidinoacetate methyltransferase deficiency", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402996483/MONDO:0012999/026/el/0/1609", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402996483/MONDO:0012999/026/ei/1/1610", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50047_EP16649150327501", "id": "CG-PCER-AGENT:CG_50047_EP16649150327501", "type": "Agent" }, "contributionDate": { "date": "2025/5/20", "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/CA402996483/MONDO:0012999/026/el/0/1609/1611", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA402996483/MONDO:0012999/026/ci/CA402996483/MONDO:0012999/026.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50047_EP16649150327501", "id": "CG-PCER-AGENT:CG_50047_EP16649150327501", "type": "Agent" }, "comments": "One proband with clinical and biochemical features consistent with GAMT deficiency is homozygous for the variant. 0.5 points (PM3_Supporting).", "contributionDate": { "date": "2025/5/20", "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": "CA402996483/MONDO:0012999/026/ci/CA402996483/MONDO:0012999/026.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA402996483/MONDO:0012999/026/0/1609/1611", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA402996483/MONDO:0012999/026/1/1610", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA402996483/MONDO:0012999/026/0/1609", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402996483/MONDO:0012999/026/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402996483/MONDO:0012999/026/ei/1/1832", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50047_EP16649150327501", "id": "CG-PCER-AGENT:CG_50047_EP16649150327501", "type": "Agent" }, "contributionDate": { "date": "2025/5/20", "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/CA402996483/MONDO:0012999/026/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA402996483/MONDO:0012999/026/ci/CA402996483/MONDO:0012999/026.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50047_EP16649150327501", "id": "CG-PCER-AGENT:CG_50047_EP16649150327501", "type": "Agent" }, "comments": "One proband who is homozygous for the variant has been reported. This individual has developmental delay and seizures, in addition to elevated guanidinoacetate in urine and plasma and low creatine in urine and plasma (PMID: 24440240) (PP4_Moderate).", "contributionDate": { "date": "2025/5/20", "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": "CA402996483/MONDO:0012999/026/ci/CA402996483/MONDO:0012999/026.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA402996483/MONDO:0012999/026/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA402996483/MONDO:0012999/026/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA402996483/MONDO:0012999/026/0/1831", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402996483/MONDO:0012999/026/el/0/1753", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402996483/MONDO:0012999/026/ei/1/1754", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50047_EP16649150327501", "id": "CG-PCER-AGENT:CG_50047_EP16649150327501", "type": "Agent" }, "contributionDate": { "date": "2025/5/20", "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/CA402996483/MONDO:0012999/026/el/0/1753/1755", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA402996483/MONDO:0012999/026/ci/CA402996483/MONDO:0012999/026.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50047_EP16649150327501", "id": "CG-PCER-AGENT:CG_50047_EP16649150327501", "type": "Agent" }, "comments": "The computational predictor REVEL gives a score of 0.943 which is >0.932, evidence that correlates with impact to GAMT function at the strong level (PMID: 36413997) (PP3_Strong). No impact on splicing is predicted by SpliceAI.", "contributionDate": { "date": "2025/5/20", "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": "CA402996483/MONDO:0012999/026/ci/CA402996483/MONDO:0012999/026.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA402996483/MONDO:0012999/026/0/1753/1755", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA402996483/MONDO:0012999/026/1/1754", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA402996483/MONDO:0012999/026/0/1753", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402996483/MONDO:0012999/026/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402996483/MONDO:0012999/026/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50047_EP16649150327501", "id": "CG-PCER-AGENT:CG_50047_EP16649150327501", "type": "Agent" }, "contributionDate": { "date": "2025/5/20", "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/CA402996483/MONDO:0012999/026/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA402996483/MONDO:0012999/026/ci/CA402996483/MONDO:0012999/026.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50047_EP16649150327501", "id": "CG-PCER-AGENT:CG_50047_EP16649150327501", "type": "Agent" }, "comments": "The highest population minor allele frequency in gnomAD v4.1.0. is 0.00003384 (3/88658 alleles) in the South Asian population, which is lower than the ClinGen CCDS VCEP’s threshold for PM2_Supporting (<0.0004), meeting this criterion (PM2_Supporting).\n", "contributionDate": { "date": "2025/5/20", "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": "CA402996483/MONDO:0012999/026/ci/CA402996483/MONDO:0012999/026.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA402996483/MONDO:0012999/026/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA402996483/MONDO:0012999/026/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA402996483/MONDO:0012999/026/0/1636", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA402996483/MONDO:0012999/026", "metadata": { "created": "2025-05-20T15:04:58.382Z", "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, 20 May 2025 15:04:58 -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": "48f2aa0e-c95d-486e-a0b6-f29bce515120", "variant": { "@id": "https://reg.genome.network/allele/CA402996483", "id": "CAR:CA402996483", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000156.6:c.268G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000156.6(GAMT):c.268G>A (p.Glu90Lys)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-26T21:18:34.355Z" } }, "status": { "code": 200, "name": "OK" } }