{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/df780bbd-6d93-4670-9d0e-121f7e0c44d9/doc/sepio/version/1.1.0", "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/CA2499225402/MONDO:0012999/026/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2499225402/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": "2025/10/7", "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/CA2499225402/MONDO:0012999/026/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2499225402/MONDO:0012999/026/ci/CA2499225402/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": "PMID: 19288536: identified in one patient with elevated plasma GAA with low creatine and elevated urine GAA with low creatine (3pts total, PP4_Mod)", "contributionDate": { "date": "2025/10/7", "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": "CA2499225402/MONDO:0012999/026/ci/CA2499225402/MONDO:0012999/026.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2499225402/MONDO:0012999/026/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2499225402/MONDO:0012999/026/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2499225402/MONDO:0012999/026/0/1831", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2499225402/MONDO:0012999/026/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2499225402/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": "2025/10/7", "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/CA2499225402/MONDO:0012999/026/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2499225402/MONDO:0012999/026/ci/CA2499225402/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 0.00002229 (1/44860 alleles) in the East Asian population, which is lower than the ClinGen CCDS VCEP’s threshold for PM2_Supporting (<0.0004), meeting this criterion (PM2_Supporting).", "contributionDate": { "date": "2025/10/7", "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": "CA2499225402/MONDO:0012999/026/ci/CA2499225402/MONDO:0012999/026.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2499225402/MONDO:0012999/026/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2499225402/MONDO:0012999/026/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2499225402/MONDO:0012999/026/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2499225402/MONDO:0012999/026/el/0/1762", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2499225402/MONDO:0012999/026/ei/1/1763", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50047_EP16649150327501", "id": "CG-PCER-AGENT:CG_50047_EP16649150327501", "type": "Agent" }, "contributionDate": { "date": "2025/10/7", "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/CA2499225402/MONDO:0012999/026/el/0/1762/1764", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2499225402/MONDO:0012999/026/ci/CA2499225402/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": "Frameshift variant in exon 5/6 in the last 50bp of the penultimate exon (c.526), such that NMD is not predicted. Predicted to result in frameshift at amino acid position 176 and premature termination at amino acid position 178/236, resulting in removal of 58 amino acids (24.5% of the protein, >10% of the protein), such that PVS1_Strong applies per CCDS specifications. ", "contributionDate": { "date": "2025/10/7", "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": "CA2499225402/MONDO:0012999/026/ci/CA2499225402/MONDO:0012999/026.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2499225402/MONDO:0012999/026/0/1762/1764", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2499225402/MONDO:0012999/026/1/1763", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2499225402/MONDO:0012999/026/0/1762", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2499225402/MONDO:0012999/026/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2499225402/MONDO:0012999/026/ei/1/1718", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50047_EP16649150327501", "id": "CG-PCER-AGENT:CG_50047_EP16649150327501", "type": "Agent" }, "contributionDate": { "date": "2025/10/7", "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/CA2499225402/MONDO:0012999/026/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2499225402/MONDO:0012999/026/ci/CA2499225402/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": "Patient 3: comp het for c.590T>C (p.L197P)/c.526delG (p.E176SfsX2); did not count for PM3 here because this occurrence was counted for PM3 for the p.L197P variant, thereby preventing circularity in use of PM3", "contributionDate": { "date": "2025/10/7", "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": "CA2499225402/MONDO:0012999/026/ci/CA2499225402/MONDO:0012999/026.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2499225402/MONDO:0012999/026/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2499225402/MONDO:0012999/026/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2499225402/MONDO:0012999/026/0/1717", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2499225402/MONDO:0012999/026", "metadata": { "created": "2025-10-07T22:40:30.071Z", "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, 07 Oct 2025 22:40:29 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.1.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "df780bbd-6d93-4670-9d0e-121f7e0c44d9", "variant": { "@id": "https://reg.genome.network/allele/CA2499225402", "id": "CAR:CA2499225402", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000156.6:c.526del" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000156.6(GAMT):c.526del (p.Glu176fs)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-28T06:29:44.187Z" } }, "status": { "code": 200, "name": "OK" } }