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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": [
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        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA913184710/MONDO:0012999/026/el/0/1636",
        "evidenceItem": [
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            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA913184710/MONDO:0012999/026/ei/1/1637",
            "contribution": [
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                  "id": "SEPIO:0000516",
                  "label": "curator role",
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                },
                "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": [
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                          "type": "Agent"
                        },
                        "comments": "Absent in population databases. ",
                        "contributionDate": {
                          "date": "2023/3/29",
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                        },
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                    ],
                    "id": "CA913184710/MONDO:0012999/026/ci/CA913184710/MONDO:0012999/026.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA913184710/MONDO:0012999/026/0/1636/1638",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA913184710/MONDO:0012999/026/1/1637",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA913184710/MONDO:0012999/026/0/1636",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA913184710/MONDO:0012999/026/el/0/1738",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA913184710/MONDO:0012999/026/ei/1/1739",
            "contribution": [
              {
                "agent": {
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                },
                "contributionRole": {
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                  "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/CA913184710/MONDO:0012999/026/el/0/1738/1740",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA913184710/MONDO:0012999/026/ci/CA913184710/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: 15108290: Identified in one proband who showed elevated urinary GAA (1pt) and partially absent creatine peak and absent GAA peak on brain MRS (3pts) with full GAMT gene sequencing (4pts total)",
                        "contributionDate": {
                          "date": "2023/3/29",
                          "description": "Date on which this evidence was provided"
                        },
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                          "id": "SEPIO:0000516",
                          "label": "curator role",
                          "type": "ContributoryRole"
                        },
                        "type": "Contribution"
                      }
                    ],
                    "id": "CA913184710/MONDO:0012999/026/ci/CA913184710/MONDO:0012999/026.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA913184710/MONDO:0012999/026/0/1738/1740",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA913184710/MONDO:0012999/026/1/1739",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA913184710/MONDO:0012999/026/0/1738",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA913184710/MONDO:0012999/026/el/0/1717",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA913184710/MONDO:0012999/026/ei/1/1718",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50047_EP16649150327501",
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                  "description": "Date on which this evidence was provided"
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                  "@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/CA913184710/MONDO:0012999/026/el/0/1717/1719",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA913184710/MONDO:0012999/026/ci/CA913184710/MONDO:0012999/026.002",
                    "contribution": [
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                          "id": "CG-PCER-AGENT:CG_50047_EP16649150327501",
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                        },
                        "comments": "Identified in at least one individual with guanidinoacetate methyltransferase deficiency, who was a compound heterozygote (PMID: 24415674, PMID: 15108290); this occurrence was not counted for PM3 so that it could be counted for PM3 for the other variant, thereby preventing circularity in use of PM3. ",
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                          "date": "2023/3/29",
                          "description": "Date on which this evidence was provided"
                        },
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                          "label": "curator role",
                          "type": "ContributoryRole"
                        },
                        "type": "Contribution"
                      }
                    ],
                    "id": "CA913184710/MONDO:0012999/026/ci/CA913184710/MONDO:0012999/026.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA913184710/MONDO:0012999/026/0/1717/1719",
                "type": "EvidenceLine"
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            ],
            "id": "CG-PCER-VARINT:CA913184710/MONDO:0012999/026/1/1718",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Not Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA913184710/MONDO:0012999/026/0/1717",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA913184710/MONDO:0012999/026/el/0/1762",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA913184710/MONDO:0012999/026/ei/1/1763",
            "contribution": [
              {
                "agent": {
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                },
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                  "date": "2023/3/29",
                  "description": "Date on which this evidence was provided"
                },
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                  "@id": "https://obofoundry.org/sepio/0000156",
                  "id": "SEPIO:0000516",
                  "label": "curator role",
                  "type": "ContributoryRole"
                },
                "type": "Contribution"
              }
            ],
            "criterion": {
              "@id": "https://obofoundry.org/sepio/clingen/0020",
              "defaultStrength": {
                "@id": "https://obofoundry.org/sepio/SEPIO:0000330",
                "id": "SEPIO:0000330",
                "label": "Pathogenic Strong"
              },
              "id": "0020",
              "label": "PVS1",
              "type": "Criterion"
            },
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA913184710/MONDO:0012999/026/el/0/1762/1764",
                "evidenceItem": [
                  {
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                        },
                        "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 191/236, resulting in removal of 45 amino acids (19.1% of the protein, >10% of the protein), such that PVS1_Strong applies per CCDS specifications. ",
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                          "date": "2023/3/29",
                          "description": "Date on which this evidence was provided"
                        },
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                          "@id": "https://obofoundry.org/sepio/0000156",
                          "id": "SEPIO:0000516",
                          "label": "curator role",
                          "type": "ContributoryRole"
                        },
                        "type": "Contribution"
                      }
                    ],
                    "id": "CA913184710/MONDO:0012999/026/ci/CA913184710/MONDO:0012999/026.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA913184710/MONDO:0012999/026/0/1762/1764",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA913184710/MONDO:0012999/026/1/1763",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA913184710/MONDO:0012999/026/0/1762",
        "type": "EvidenceLine"
      }
    ],
    "id": "CG-PCER-VARINT:CA913184710/MONDO:0012999/026",
    "metadata": {
      "created": "2024-09-28T01:31:19.478Z",
      "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 01:31:19 -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": "2b6ecaf4-3191-458c-80c0-9dfdabed4486",
    "variant": {
      "@id": "https://reg.genome.network/allele/CA913184710",
      "id": "CAR:CA913184710",
      "relatedContextualAllele": [
        {
          "alleleName": [
            {
              "name": "NM_000156.6:c.526dup"
            }
          ],
          "preferred": true
        }
      ],
      "relatedIdentifier": [
        {
          "label": "NM_000156.6(GAMT):c.526dup (p.Glu176fs)"
        }
      ],
      "type": "CAR"
    }
  },
  "metadata": {
    "rendered": {
      "by": "https://erepo.genome.network/evrepo/api/summary/srvc",
      "when": "2026-11-03T11:23:22.224Z"
    }
  },
  "status": {
    "code": 200,
    "name": "OK"
  }
}