{
  "data": {
    "@context": "https://erepo.genome.network/evrepo/api/context",
    "@id": "https://cgerepoapi/evrepo/api/summary/classification/4e4553fb-c35a-404e-a0ad-de1af2055bab/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/CA9043673/MONDO:0012999/026/el/0/1636",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA9043673/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": "2023/5/25",
                  "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/CA9043673/MONDO:0012999/026/el/0/1636/1638",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA9043673/MONDO:0012999/026/ci/CA9043673/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 0.00003 in the South Asian population, which is lower than the ClinGen CCDS VCEP's threshold for PM2_Supporting, meeting this criterion (PM2_Supporting).",
                        "contributionDate": {
                          "date": "2023/5/25",
                          "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": "CA9043673/MONDO:0012999/026/ci/CA9043673/MONDO:0012999/026.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA9043673/MONDO:0012999/026/0/1636/1638",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA9043673/MONDO:0012999/026/1/1637",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA9043673/MONDO:0012999/026/0/1636",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA9043673/MONDO:0012999/026/el/0/1738",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA9043673/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": "2023/5/25",
                  "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/CA9043673/MONDO:0012999/026/el/0/1738/1740",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA9043673/MONDO:0012999/026/ci/CA9043673/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 8 (Table 2) is a male, diagnosed with GAMT deficiency at 14 years old; serum creatine (pre-treatment) 4.2 uM/L (normal range) 34–130 uM/L; serum GAA (pre-treatment 33.3 uM/L (normal range 0.7–5.4 uM/L)(2 points); on MRS he had a decreased creatine peak with slight elevation of GAA peak (3 points) (PMID: 19027335). Full GAMT gene sequencing done. ",
                        "contributionDate": {
                          "date": "2023/5/25",
                          "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": "CA9043673/MONDO:0012999/026/ci/CA9043673/MONDO:0012999/026.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA9043673/MONDO:0012999/026/0/1738/1740",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA9043673/MONDO:0012999/026/1/1739",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA9043673/MONDO:0012999/026/0/1738",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA9043673/MONDO:0012999/026/el/0/1717",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA9043673/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": "2023/5/25",
                  "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/CA9043673/MONDO:0012999/026/el/0/1717/1719",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA9043673/MONDO:0012999/026/ci/CA9043673/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 8 is compound heterozygous for the variant and c.610_611delAGinsGAA (p.Arg204GlufsTer63), phase unknown. The in trans data from this patient will be used in the assessment of c.610_611delAGinsGAA and is not included here to avoid circular logic.",
                        "contributionDate": {
                          "date": "2023/5/25",
                          "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": "CA9043673/MONDO:0012999/026/ci/CA9043673/MONDO:0012999/026.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA9043673/MONDO:0012999/026/0/1717/1719",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA9043673/MONDO:0012999/026/1/1718",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Not Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA9043673/MONDO:0012999/026/0/1717",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA9043673/MONDO:0012999/026/el/0/1594",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA9043673/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": "2023/5/25",
                  "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/CA9043673/MONDO:0012999/026/el/0/1594/1596",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA9043673/MONDO:0012999/026/ci/CA9043673/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.402C>G (p.Tyr134Ter) variant in GAMT is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 4/6 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1).",
                        "contributionDate": {
                          "date": "2023/5/25",
                          "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": "CA9043673/MONDO:0012999/026/ci/CA9043673/MONDO:0012999/026.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA9043673/MONDO:0012999/026/0/1594/1596",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA9043673/MONDO:0012999/026/1/1595",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA9043673/MONDO:0012999/026/0/1594",
        "type": "EvidenceLine"
      }
    ],
    "id": "CG-PCER-VARINT:CA9043673/MONDO:0012999/026",
    "metadata": {
      "created": "2024-09-28T02:00:39.362Z",
      "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 02:00:39 -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": "4e4553fb-c35a-404e-a0ad-de1af2055bab",
    "variant": {
      "@id": "https://reg.genome.network/allele/CA9043673",
      "id": "CAR:CA9043673",
      "relatedContextualAllele": [
        {
          "alleleName": [
            {
              "name": "NM_000156.6:c.402C>G"
            }
          ],
          "preferred": true
        }
      ],
      "relatedIdentifier": [
        {
          "label": "NM_000156.6(GAMT):c.402C>G (p.Tyr134Ter)"
        }
      ],
      "type": "CAR"
    }
  },
  "metadata": {
    "rendered": {
      "by": "https://erepo.genome.network/evrepo/api/summary/srvc",
      "when": "2026-11-02T14:09:59.752Z"
    }
  },
  "status": {
    "code": 200,
    "name": "OK"
  }
}