{
  "data": {
    "@context": "https://erepo.genome.network/evrepo/api/context",
    "@id": "https://erepo.genome.network/evrepo/api/summary/classification/bd348752-8812-41c2-8014-b97f14b9dff5/doc/sepio/version/1.0.0",
    "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 1.1.0",
      "type": "VariantPathogenicityInterpretationGuideline",
      "version": "1.1.0"
    },
    "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/CA9043720/MONDO:0012999/026/el/0/1594",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA9043720/MONDO:0012999/026/ei/1/1595",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50047_EP16649150327501",
                  "id": "CG-PCER-AGENT:CG_50047_EP16649150327501",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2023/3/9",
                  "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/0017",
              "defaultStrength": {
                "@id": "https://obofoundry.org/sepio/SEPIO:0000220",
                "id": "SEPIO:0000220",
                "label": "Pathogenic Very Strong"
              },
              "id": "0017",
              "label": "PVS1",
              "type": "Criterion"
            },
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA9043720/MONDO:0012999/026/el/0/1594/1596",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA9043720/MONDO:0012999/026/ci/CA9043720/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 NM_000156.6:c.328-1G>A variant in GAMT occurs within the canonical splice acceptor site of intron 2. It is predicted to cause skipping of biologically-relevant-exon 3/6, resulting in a frameshift leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). ",
                        "contributionDate": {
                          "date": "2023/3/9",
                          "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": "CA9043720/MONDO:0012999/026/ci/CA9043720/MONDO:0012999/026.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA9043720/MONDO:0012999/026/0/1594/1596",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA9043720/MONDO:0012999/026/1/1595",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA9043720/MONDO:0012999/026/0/1594",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA9043720/MONDO:0012999/026/el/0/1636",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA9043720/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": "2023/3/9",
                  "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/0030",
              "defaultStrength": {
                "@id": "https://obofoundry.org/sepio/SEPIO:0000329",
                "id": "SEPIO:0000329",
                "label": "Pathogenic Supporting"
              },
              "id": "0030",
              "label": "PM2",
              "type": "Criterion"
            },
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA9043720/MONDO:0012999/026/el/0/1636/1638",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA9043720/MONDO:0012999/026/ci/CA9043720/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 v2.1.1 is [0.00006] (1/15792 alleles) in the African population, which is lower than the ClinGen CCDS VCEP’s threshold for PM2_Supporting (<0.0004), meeting this criterion (PM2_Supporting). SpliceAI indocates that this variant abolishes splicing but also that a new aceptor site may be created 1 nucleotide upstream. Even if this new site is used, the consequence would still be a frameshift. ",
                        "contributionDate": {
                          "date": "2023/3/9",
                          "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": "CA9043720/MONDO:0012999/026/ci/CA9043720/MONDO:0012999/026.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA9043720/MONDO:0012999/026/0/1636/1638",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA9043720/MONDO:0012999/026/1/1637",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA9043720/MONDO:0012999/026/0/1636",
        "type": "EvidenceLine"
      }
    ],
    "id": "CG-PCER-VARINT:CA9043720/MONDO:0012999/026",
    "metadata": {
      "created": "2024-09-28T01:21:38.570Z",
      "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": "Sat, 28 Sep 2024 01:21:38 -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": "bd348752-8812-41c2-8014-b97f14b9dff5",
    "variant": {
      "@id": "https://reg.genome.network/allele/CA9043720",
      "id": "CAR:CA9043720",
      "relatedContextualAllele": [
        {
          "alleleName": [
            {
              "name": "NM_000156.6:c.328-1G>A"
            }
          ],
          "preferred": true
        }
      ],
      "relatedIdentifier": [
        {
          "label": "NM_000156.6(GAMT):c.328-1G>A"
        }
      ],
      "type": "CAR"
    }
  },
  "metadata": {
    "rendered": {
      "by": "https://erepo.genome.network/evrepo/api/summary/srvc",
      "when": "2026-04-08T10:54:53.491Z"
    }
  },
  "status": {
    "code": 200,
    "name": "OK"
  }
}