{
  "data": {
    "@context": "https://erepo.genome.network/evrepo/api/context",
    "@id": "https://cgerepoapi/evrepo/api/summary/classification/70289cf1-f13c-4317-b172-1ab3d6434b82/doc/sepio/version/2.0.0",
    "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 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/CA402990982/MONDO:0012999/026/el/0/1690",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402990982/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": "2025/12/10",
                  "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/CA402990982/MONDO:0012999/026/el/0/1690/1692",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA402990982/MONDO:0012999/026/ci/CA402990982/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 0.925 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). No impact on splicing was predicted by SpliceAI.\n",
                        "contributionDate": {
                          "date": "2025/12/10",
                          "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": "CA402990982/MONDO:0012999/026/ci/CA402990982/MONDO:0012999/026.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA402990982/MONDO:0012999/026/0/1690/1692",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA402990982/MONDO:0012999/026/1/1691",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA402990982/MONDO:0012999/026/0/1690",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402990982/MONDO:0012999/026/el/0/1696",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402990982/MONDO:0012999/026/ei/1/1697",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50047_EP16649150327501",
                  "id": "CG-PCER-AGENT:CG_50047_EP16649150327501",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2025/12/10",
                  "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/CA402990982/MONDO:0012999/026/el/0/1696/1698",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA402990982/MONDO:0012999/026/ci/CA402990982/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": "Expression of the variant in GAMT-deficient human fibroblast cell line resulted in <5% wild type GAMT activity indicating that this variant may impact protein function (PMID: 24415674) (PS3_Supporting)",
                        "contributionDate": {
                          "date": "2025/12/10",
                          "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": "CA402990982/MONDO:0012999/026/ci/CA402990982/MONDO:0012999/026.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA402990982/MONDO:0012999/026/0/1696/1698",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA402990982/MONDO:0012999/026/1/1697",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA402990982/MONDO:0012999/026/0/1696",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402990982/MONDO:0012999/026/el/0/1636",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402990982/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": "2025/12/10",
                  "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/CA402990982/MONDO:0012999/026/el/0/1636/1638",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA402990982/MONDO:0012999/026/ci/CA402990982/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 0.00000339 (4/1179854 alleles) in the European non-Finnish population, which is lower than the ClinGen CCDS VCEP’s threshold for PM2_Supporting (<0.0004), meeting this criterion (PM2_Supporting).\n",
                        "contributionDate": {
                          "date": "2025/12/10",
                          "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": "CA402990982/MONDO:0012999/026/ci/CA402990982/MONDO:0012999/026.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA402990982/MONDO:0012999/026/0/1636/1638",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA402990982/MONDO:0012999/026/1/1637",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA402990982/MONDO:0012999/026/0/1636",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402990982/MONDO:0012999/026/el/0/1738",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402990982/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": "2025/12/10",
                  "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/CA402990982/MONDO:0012999/026/el/0/1738/1740",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA402990982/MONDO:0012999/026/ci/CA402990982/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": "Two patients with this variant had elevated guanidinoacetate with low creatine in plasma and elevated guanidinoacetate with low creatine in urine; one of these individuals had a brain MRS which revealed no creatine peak (PMID: 16293431, 19288536). ",
                        "contributionDate": {
                          "date": "2025/12/10",
                          "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": "CA402990982/MONDO:0012999/026/ci/CA402990982/MONDO:0012999/026.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA402990982/MONDO:0012999/026/0/1738/1740",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA402990982/MONDO:0012999/026/1/1739",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA402990982/MONDO:0012999/026/0/1738",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402990982/MONDO:0012999/026/el/0/1717",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA402990982/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": "2025/12/10",
                  "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/CA402990982/MONDO:0012999/026/el/0/1717/1719",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA402990982/MONDO:0012999/026/ci/CA402990982/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": "One patient was reported to be compound heterozygous for the variant and another variant in GAMT that has been classified as likely pathogenic by the ClinGen CCDS VCEP, c.526delG; the phase was confirmed by parental testing (PMID: 19288536, 19461121) (1 point). Another patient was reported to be homozygous for the variant PMID: 16293431 (0.5 points). Total 1.5 points (PM3)",
                        "contributionDate": {
                          "date": "2025/12/10",
                          "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": "CA402990982/MONDO:0012999/026/ci/CA402990982/MONDO:0012999/026.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA402990982/MONDO:0012999/026/0/1717/1719",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA402990982/MONDO:0012999/026/1/1718",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA402990982/MONDO:0012999/026/0/1717",
        "type": "EvidenceLine"
      }
    ],
    "id": "CG-PCER-VARINT:CA402990982/MONDO:0012999/026",
    "metadata": {
      "created": "2025-12-10T20:21:36.979Z",
      "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, 10 Dec 2025 20:21:36 -0000",
      "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)",
      "version": "2.0.0"
    },
    "statementOutcome": {
      "@id": "https://loinc.org/LA6668-3",
      "id": "LN:LA6668-3",
      "label": "Pathogenic"
    },
    "type": "VariantPathogenicityInterpretation",
    "uuid": "70289cf1-f13c-4317-b172-1ab3d6434b82",
    "variant": {
      "@id": "https://reg.genome.network/allele/CA402990982",
      "id": "CAR:CA402990982",
      "relatedContextualAllele": [
        {
          "alleleName": [
            {
              "name": "NM_000156.6:c.590T>C"
            }
          ],
          "preferred": true
        }
      ],
      "relatedIdentifier": [
        {
          "label": "NM_000156.6:c.590T>C"
        }
      ],
      "type": "CAR"
    }
  },
  "metadata": {
    "rendered": {
      "by": "https://erepo.genome.network/evrepo/api/summary/srvc",
      "when": "2026-10-29T14:27:00.549Z"
    }
  },
  "status": {
    "code": 200,
    "name": "OK"
  }
}