{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/df177d38-29ce-4a53-8bc0-8131ab4fe8da/doc/sepio/version/1.2.0", "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/CA402998035/MONDO:0012999/026/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402998035/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": "2025/10/8", "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/CA402998035/MONDO:0012999/026/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA402998035/MONDO:0012999/026/ci/CA402998035/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 variant is absent in gnomAD v4.1.0. (PM2_Supporting).", "contributionDate": { "date": "2025/10/8", "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": "CA402998035/MONDO:0012999/026/ci/CA402998035/MONDO:0012999/026.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA402998035/MONDO:0012999/026/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA402998035/MONDO:0012999/026/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA402998035/MONDO:0012999/026/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402998035/MONDO:0012999/026/el/0/1738", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402998035/MONDO:0012999/026/ei/1/1739", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50047_EP16649150327501", "id": "CG-PCER-AGENT:CG_50047_EP16649150327501", "type": "Agent" }, "contributionDate": { "date": "2025/10/8", "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/CA402998035/MONDO:0012999/026/el/0/1738/1740", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA402998035/MONDO:0012999/026/ci/CA402998035/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": "Identified in one individual who showed elevated urinary GAA (1pt), GAMT enzymatic activity <0.1 nmol/h/mg in lymphoblasts (3pts), with full GAMT gene sequencing performed (PMID: 15108290) (total - 4pts, PP4_Strong). Two additional individuals have been reported with clinical symptoms consistent with GAMT deficiency but no biochemical or MRS data is available (PMID: 38020815, 39006040).", "contributionDate": { "date": "2025/10/8", "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": "CA402998035/MONDO:0012999/026/ci/CA402998035/MONDO:0012999/026.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA402998035/MONDO:0012999/026/0/1738/1740", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA402998035/MONDO:0012999/026/1/1739", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA402998035/MONDO:0012999/026/0/1738", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402998035/MONDO:0012999/026/el/0/1690", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402998035/MONDO:0012999/026/ei/1/1691", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50047_EP16649150327501", "id": "CG-PCER-AGENT:CG_50047_EP16649150327501", "type": "Agent" }, "contributionDate": { "date": "2025/10/8", "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/CA402998035/MONDO:0012999/026/el/0/1690/1692", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA402998035/MONDO:0012999/026/ci/CA402998035/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 0.894 which is in the range of 0.773-0.932, evidence that correlates with impact to GAMT function at the moderate level (PMID: 36413997) (PP3_Moderate).\n", "contributionDate": { "date": "2025/10/8", "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": "CA402998035/MONDO:0012999/026/ci/CA402998035/MONDO:0012999/026.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA402998035/MONDO:0012999/026/0/1690/1692", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA402998035/MONDO:0012999/026/1/1691", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA402998035/MONDO:0012999/026/0/1690", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402998035/MONDO:0012999/026/el/0/1609", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402998035/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": "2025/10/8", "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/CA402998035/MONDO:0012999/026/el/0/1609/1611", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA402998035/MONDO:0012999/026/ci/CA402998035/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": "Identified in one homozygous proband, in cis with two benign variants (c.626C>T (p.Thr209Met) (ClinVar ID: 21068) and c.459+71G>A (ClinVar ID: 21067)) (PMID: 15108290) (0.5 points). Two additional homozygous probands have been identified with clinical symptoms consistent with GAMT deficiency. However, because no biochemical or MRS data is available, this data was not included (PMID: 38020815, 39006040). Total 0.5 points (PM3_Supporting)", "contributionDate": { "date": "2025/10/8", "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": "CA402998035/MONDO:0012999/026/ci/CA402998035/MONDO:0012999/026.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA402998035/MONDO:0012999/026/0/1609/1611", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA402998035/MONDO:0012999/026/1/1610", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA402998035/MONDO:0012999/026/0/1609", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA402998035/MONDO:0012999/026", "metadata": { "created": "2025-10-08T21:42:00.265Z", "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": "Wed, 08 Oct 2025 21:41:59 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.2.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "df177d38-29ce-4a53-8bc0-8131ab4fe8da", "variant": { "@id": "https://reg.genome.network/allele/CA402998035", "id": "CAR:CA402998035", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_138924.3:c.160G>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_138924.3:c.160G>C" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-29T17:24:17.666Z" } }, "status": { "code": 200, "name": "OK" } }