{ "data": [ { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/d8d2e477-0bfe-4136-9489-617a94f7fda6/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/CA114364/MONDO:0009861/006/el/0/1798", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA114364/MONDO:0009861/006/ei/1/1799", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "contributionDate": { "date": "2019/4/5", "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/CA114364/MONDO:0009861/006/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA114364/MONDO:0009861/006/ci/CA114364/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": "Extremely low frequency in ExAC and GnomAD (MAF=0.00036) and absent from 1000G and ESP", "contributionDate": { "date": "2019/4/5", "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": "CA114364/MONDO:0009861/006/ci/CA114364/MONDO:0009861/006.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA114364/MONDO:0009861/006/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA114364/MONDO:0009861/006/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA114364/MONDO:0009861/006/0/1798", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA114364/MONDO:0009861/006/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA114364/MONDO:0009861/006/ei/1/1832", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "contributionDate": { "date": "2019/4/5", "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/0018", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "0018", "label": "PP4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA114364/MONDO:0009861/006/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA114364/MONDO:0009861/006/ci/EV000000065", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "Haplotype analysis at the PAH locus was performed in 17 Danish families with non-PKU HPA, revealing compound heterozygosity in all individuals. 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11G>A (VarID607, Pathogenic) + D415N", "contributionDate": { "date": "2019/4/5", "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": "CA114364/MONDO:0009861/006/ci/EV000000064", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/18299955", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA114364/MONDO:0009861/006/ci/EV000000065", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "D415N was found in trans with R408W (VarID 577, Pathogenic) in 1 HPA patient.", "contributionDate": { "date": "2019/4/5", "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": "CA114364/MONDO:0009861/006/ci/EV000000065", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/1358789", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA114364/MONDO:0009861/006/ci/EV000000039", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "Patient 4: F39L (VarID 605, Pathogenic)/D415N; Patient 5:Y414C (VarID 593, Pathogenic)/D415N.", "contributionDate": { "date": "2019/4/5", "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": "CA114364/MONDO:0009861/006/ci/EV000000039", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/12501224", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA114364/MONDO:0009861/006/0/1669/1671", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA114364/MONDO:0009861/006/1/1670", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA114364/MONDO:0009861/006/0/1669", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA114364/MONDO:0009861/006/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA114364/MONDO:0009861/006/ei/1/1829", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "contributionDate": { "date": "2019/4/5", "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/0052", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0052", "label": "PS3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA114364/MONDO:0009861/006/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA114364/MONDO:0009861/006/ci/EV000000051", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "We have used two heterologous in vitro expression systems (a mammalian cell-free transcription-translation system and the pET system of Escherichia coli) to examine 34 mutations that have been associated with PAH deficiency in the Danish population. D415N had PAH enzyme activity of 128/100% of wt in the pcDNA3/IVT system and 72+/-19 in the pET/E. coli system.", "contributionDate": { "date": "2019/4/5", "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": "CA114364/MONDO:0009861/006/ci/EV000000051", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/11161839", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA114364/MONDO:0009861/006/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA114364/MONDO:0009861/006/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA114364/MONDO:0009861/006/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA114364/MONDO:0009861/006/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA114364/MONDO:0009861/006/ei/1/1781", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "contributionDate": { "date": "2019/4/5", "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/008", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "008", "label": "PM5", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA114364/MONDO:0009861/006/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA114364/MONDO:0009861/006/ci/CA114364/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": "Only variant in this codon in ClinVar", "contributionDate": { "date": "2019/4/5", "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": "CA114364/MONDO:0009861/006/ci/CA114364/MONDO:0009861/006.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA114364/MONDO:0009861/006/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA114364/MONDO:0009861/006/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA114364/MONDO:0009861/006/0/1780", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA114364/MONDO:0009861/006", "metadata": { "created": "2024-09-27T19:41:00.241Z", "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": "Fri, 27 Sep 2024 19:41:00 -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": "d8d2e477-0bfe-4136-9489-617a94f7fda6", "variant": { "@id": "https://reg.genome.network/allele/CA114364", "id": "CAR:CA114364", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000277.1:c.1243G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000277.1(PAH):c.1243G>A (p.Asp415Asn)" } ], "type": "CAR" } } ], "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-01T10:04:24.824Z" } }, "status": { "code": 200, "name": "OK" } }