{
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    "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/CA402998364/MONDO:0012999/026/el/0/1798",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402998364/MONDO:0012999/026/ei/1/1799",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50047_EP16649150327501",
                  "id": "CG-PCER-AGENT:CG_50047_EP16649150327501",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2023/9/13",
                  "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/CA402998364/MONDO:0012999/026/el/0/1798/1800",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA402998364/MONDO:0012999/026/ci/CA402998364/MONDO:0012999/026.002",
                    "contribution": [
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                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50047_EP16649150327501",
                          "id": "CG-PCER-AGENT:CG_50047_EP16649150327501",
                          "type": "Agent"
                        },
                        "comments": "This variant is absent in gnomAD v2.1.1 but coverage of this region is <20X and therefore PM2_Supporting is not met.",
                        "contributionDate": {
                          "date": "2023/9/13",
                          "description": "Date on which this evidence was provided"
                        },
                        "contributionRole": {
                          "@id": "https://obofoundry.org/sepio/0000156",
                          "id": "SEPIO:0000516",
                          "label": "curator role",
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                        "type": "Contribution"
                      }
                    ],
                    "id": "CA402998364/MONDO:0012999/026/ci/CA402998364/MONDO:0012999/026.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA402998364/MONDO:0012999/026/0/1798/1800",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA402998364/MONDO:0012999/026/1/1799",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Not Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA402998364/MONDO:0012999/026/0/1798",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402998364/MONDO:0012999/026/el/0/1594",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402998364/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": "2023/9/13",
                  "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/CA402998364/MONDO:0012999/026/el/0/1594/1596",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA402998364/MONDO:0012999/026/ci/CA402998364/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.48C>A (p.Cys16Ter) variant in GAMT is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 1/6 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1).",
                        "contributionDate": {
                          "date": "2023/9/13",
                          "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": "CA402998364/MONDO:0012999/026/ci/CA402998364/MONDO:0012999/026.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA402998364/MONDO:0012999/026/0/1594/1596",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA402998364/MONDO:0012999/026/1/1595",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA402998364/MONDO:0012999/026/0/1594",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402998364/MONDO:0012999/026/el/0/1738",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402998364/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": "2023/9/13",
                  "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/005",
              "defaultStrength": {
                "@id": "https://obofoundry.org/sepio/SEPIO:0000330",
                "id": "SEPIO:0000330",
                "label": "Pathogenic Strong"
              },
              "id": "005",
              "label": "PP4",
              "type": "Criterion"
            },
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402998364/MONDO:0012999/026/el/0/1738/1740",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA402998364/MONDO:0012999/026/ci/CA402998364/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": "First cousins, who are homozygous for the variant, have been reported. One of these individuals had elevated guanidinoacetate in urine and decreased creatine peak on MRS (PP4_Strong).",
                        "contributionDate": {
                          "date": "2023/9/13",
                          "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": "CA402998364/MONDO:0012999/026/ci/CA402998364/MONDO:0012999/026.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA402998364/MONDO:0012999/026/0/1738/1740",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA402998364/MONDO:0012999/026/1/1739",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA402998364/MONDO:0012999/026/0/1738",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402998364/MONDO:0012999/026/el/0/1717",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402998364/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": "2023/9/13",
                  "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/007",
              "defaultStrength": {
                "@id": "https://obofoundry.org/sepio/SEPIO:0000216",
                "id": "SEPIO:0000216",
                "label": "Pathogenic Moderate"
              },
              "id": "007",
              "label": "PM3",
              "type": "Criterion"
            },
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402998364/MONDO:0012999/026/el/0/1717/1719",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA402998364/MONDO:0012999/026/ci/CA402998364/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": "First cousins who are homozygous for the variant (PMID 31559727; 0.5 points), and siblings who are compound heterozygous for the variant and another variant in GAMT that has been classified as pathogenic by the ClinGen CCDS VCEP, c.327G>A, phase unknown, have been reported (PMID: 24268530; 0.5 points). Total 1 point (PM3).",
                        "contributionDate": {
                          "date": "2023/9/13",
                          "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": "CA402998364/MONDO:0012999/026/ci/CA402998364/MONDO:0012999/026.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA402998364/MONDO:0012999/026/0/1717/1719",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA402998364/MONDO:0012999/026/1/1718",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA402998364/MONDO:0012999/026/0/1717",
        "type": "EvidenceLine"
      }
    ],
    "id": "CG-PCER-VARINT:CA402998364/MONDO:0012999/026",
    "metadata": {
      "created": "2024-09-28T02:51:04.740Z",
      "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 02:51:04 -0000",
      "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)",
      "version": "1.0.0"
    },
    "statementOutcome": {
      "@id": "https://loinc.org/LA6668-3",
      "id": "LN:LA6668-3",
      "label": "Pathogenic"
    },
    "type": "VariantPathogenicityInterpretation",
    "uuid": "3a761134-fdab-4d0f-a4da-dcb7b040a030",
    "variant": {
      "@id": "https://reg.genome.network/allele/CA402998364",
      "id": "CAR:CA402998364",
      "relatedContextualAllele": [
        {
          "alleleName": [
            {
              "name": "NM_138924.3:c.48C>A"
            }
          ],
          "preferred": true
        }
      ],
      "relatedIdentifier": [
        {
          "label": "NM_138924.3:c.48C>A"
        }
      ],
      "type": "CAR"
    }
  },
  "metadata": {
    "rendered": {
      "by": "https://erepo.genome.network/evrepo/api/summary/srvc",
      "when": "2026-10-31T12:11:24.456Z"
    }
  },
  "status": {
    "code": 200,
    "name": "OK"
  }
}