{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://erepo.genome.network/evrepo/api/summary/classification/0a96804f-a9d8-44e3-aa66-b85b0dbe231d/doc/sepio/version/1.0.0", "assertionMethod": { "type": "VariantPathogenicityInterpretationGuideline" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0009861", "id": "MONDO:0009861", "label": "phenylketonuria", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229861/MONDO:0009861/006/el/0/1588", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229861/MONDO:0009861/006/ei/1/1589", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "contributionDate": { "date": "2023/7/23", "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/0072", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000328", "id": "SEPIO:0000328", "label": "Benign Strong" }, "id": "0072", "label": "BS3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229861/MONDO:0009861/006/el/0/1588/1590", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA229861/MONDO:0009861/006/ci/CA229861/MONDO:0009861/006.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "Mutation ID#11 with residual enzyme activity 32%", "contributionDate": { "date": "2023/7/23", "description": "Date on which this evidence 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"type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229861/MONDO:0009861/006/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA229861/MONDO:0009861/006/ci/CA229861/MONDO:0009861/006.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "Of these individuals, two had plasma phenylalanine >120 μmol/L with the exclusion of a defect of BH4 cofactor metabolism (PP4_Moderate) (PMID: 10234516, PMID: 23500595).", "contributionDate": { "date": "2023/7/23", "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": "CA229861/MONDO:0009861/006/ci/CA229861/MONDO:0009861/006.002", "type": 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c.937G>C (p.Ala313Pro) is path (1 submitter)", "contributionDate": { "date": "2023/7/23", "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": "CA229861/MONDO:0009861/006/ci/CA229861/MONDO:0009861/006.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA229861/MONDO:0009861/006/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA229861/MONDO:0009861/006/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA229861/MONDO:0009861/006/0/1780", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229861/MONDO:0009861/006/el/0/1636", "evidenceItem": [ { "@id": 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", "contributionDate": { "date": "2023/7/23", "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": "CA229861/MONDO:0009861/006/ci/CA229861/MONDO:0009861/006.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA229861/MONDO:0009861/006/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA229861/MONDO:0009861/006/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA229861/MONDO:0009861/006/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229861/MONDO:0009861/006/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229861/MONDO:0009861/006/ei/1/1685", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "contributionDate": { "date": "2023/7/23", "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/0080", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000327", "id": "SEPIO:0000327", "label": "Benign Supporting" }, "id": "0080", "label": "BP4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229861/MONDO:0009861/006/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA229861/MONDO:0009861/006/ci/CA229861/MONDO:0009861/006.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "All predictors suggest damaging effect. REVEL =0.907", "contributionDate": { "date": "2023/7/23", "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": "CA229861/MONDO:0009861/006/ci/CA229861/MONDO:0009861/006.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA229861/MONDO:0009861/006/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA229861/MONDO:0009861/006/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA229861/MONDO:0009861/006/0/1684", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229861/MONDO:0009861/006/el/0/1651", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229861/MONDO:0009861/006/ei/1/1652", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "contributionDate": { "date": "2023/7/23", "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/0058", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0058", "label": "PM3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229861/MONDO:0009861/006/el/0/1651/1653", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA229861/MONDO:0009861/006/ci/CA229861/MONDO:0009861/006.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "This variant has been detected in at least 8 unrelated individuals with PAH deficiency (PMID: 32668217, PMID: 27121329, PMID: 33465300, PMID: 10234516, PMID: 23500595). Of these individuals, 6 were compound heterozygotes for the variant and pathogenic variants, p.Ala104Asp, c.1066-11G>A, p.Arg408Trp, p.Ex5del4232ins268, p.Gln267Ter, in unknown phase (PMID: 32668217, PMID: 27121329, PMID: 33465300) (3pts total, PM3_Strong). ", "contributionDate": { "date": "2023/7/23", "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": "CA229861/MONDO:0009861/006/ci/CA229861/MONDO:0009861/006.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA229861/MONDO:0009861/006/0/1651/1653", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA229861/MONDO:0009861/006/1/1652", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA229861/MONDO:0009861/006/0/1651", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229861/MONDO:0009861/006/el/0/1690", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229861/MONDO:0009861/006/ei/1/1691", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "contributionDate": { "date": "2023/7/23", "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/0025", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "0025", "label": "PP3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229861/MONDO:0009861/006/el/0/1690/1692", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA229861/MONDO:0009861/006/ci/CA229861/MONDO:0009861/006.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "The computational predictor REVEL gives a score of 0.907 which is above the threshold of 0.75, evidence that correlates with impact to PAH function (PP3_Moderate). ", "contributionDate": { "date": "2023/7/23", "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": "CA229861/MONDO:0009861/006/ci/CA229861/MONDO:0009861/006.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA229861/MONDO:0009861/006/0/1690/1692", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA229861/MONDO:0009861/006/1/1691", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA229861/MONDO:0009861/006/0/1690", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA229861/MONDO:0009861/006", "metadata": { "created": "2024-09-28T02:19:08.362Z", "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 02:19:08 -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": "0a96804f-a9d8-44e3-aa66-b85b0dbe231d", "variant": { "@id": "https://reg.genome.network/allele/CA229861", "id": "CAR:CA229861", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000277.3:c.938C>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000277.3(PAH):c.938C>T (p.Ala313Val)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-04-12T13:04:23.732Z" } }, "status": { "code": 200, "name": "OK" } }