{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/c54336ad-7a33-4a07-895c-275c08ab017c/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/CA16020812/MONDO:0009861/006/el/0/1798", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16020812/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": "2021/2/12", "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/CA16020812/MONDO:0009861/006/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA16020812/MONDO:0009861/006/ci/CA16020812/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": "MAF=0.00006 in ENF gnomAD population.", "contributionDate": { "date": "2021/2/12", "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": "CA16020812/MONDO:0009861/006/ci/CA16020812/MONDO:0009861/006.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA16020812/MONDO:0009861/006/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA16020812/MONDO:0009861/006/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA16020812/MONDO:0009861/006/0/1798", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16020812/MONDO:0009861/006/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16020812/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": "2021/2/12", "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/CA16020812/MONDO:0009861/006/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA16020812/MONDO:0009861/006/ci/EV000000068", "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, probably MHP (lost to follow-up). All patients had PKU according to biochemical criteria.", "contributionDate": { "date": "2021/2/12", "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": "CA16020812/MONDO:0009861/006/ci/EV000000068", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/26542770", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA16020812/MONDO:0009861/006/ci/EV000000041", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "A total of 796 unrelated patients from 29 separate newborn screening centres of China were enrolled. These patients were diagnosed at birth either through a neonatal screening program or based on clinical presentation. Demographic data, including age, consanguinity, family history, and geographical origin, and biochemical testing data, including plasma phenylalanine (Phe) levels, dihydropteridine reductase activity, urinary biopterin and neopterin ratio, and tetrahydrobiopterin loading, were collected. One patient had c.532G>A (p.E178K).", "contributionDate": { "date": "2021/2/12", "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": "CA16020812/MONDO:0009861/006/ci/EV000000041", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/26503515", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA16020812/MONDO:0009861/006/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA16020812/MONDO:0009861/006/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA16020812/MONDO:0009861/006/0/1831", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16020812/MONDO:0009861/006/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16020812/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": "2021/2/12", "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/CA16020812/MONDO:0009861/006/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA16020812/MONDO:0009861/006/ci/EV000001264", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "We performed site-directed mutagenesis and in vitro expression (E. coli and HEK293T). The mRNA and protein levels of three variants were compared with that of wild type gene, as well as a common PAH mutation, p.R243Q, which is known to decrease protein expression and enzyme activity (Pey et al., 2003). Table 2: E178K mRNA 0.973 ± 0.181, empty control 0, wt 1.0. The lower expression in mutant groups indicated that PAH protein expression was impaired by variants. In general, all four mutations did not affect the transcription of the PAH gene, however, PAH protein synthesis and/or stability was disturbed. Exact numbers or % of wt were not reported.", "contributionDate": { "date": "2021/2/12", "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": "CA16020812/MONDO:0009861/006/ci/EV000001264", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/29653233", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA16020812/MONDO:0009861/006/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA16020812/MONDO:0009861/006/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA16020812/MONDO:0009861/006/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16020812/MONDO:0009861/006/el/0/1651", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16020812/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": "2021/2/12", "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/CA16020812/MONDO:0009861/006/el/0/1651/1653", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA16020812/MONDO:0009861/006/ci/EV000000778", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "Patient 496: IVS4-1G＞A/p.Glu178Lys. Peripheral blood samples were collected from the patients and parents in each of the 643 core families. To determine sequence variability, variable sites in patient genes were aligned with the corresponding sites from the respective parents.", "contributionDate": { "date": "2021/2/12", "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": "CA16020812/MONDO:0009861/006/ci/EV000000778", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/29316886", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA16020812/MONDO:0009861/006/ci/EV000000068", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "detected in trans with F39del. Parental testing confirmed that the two mutations identified in the 368 patients all were present in trans.", "contributionDate": { "date": "2021/2/12", "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": "CA16020812/MONDO:0009861/006/ci/EV000000068", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/26542770", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA16020812/MONDO:0009861/006/ci/EV000000699", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "Sample NBS47: c.1222C>T (R408W,P)/c.532G>A. Parental testing not performed.", "contributionDate": { "date": "2021/2/12", "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": "CA16020812/MONDO:0009861/006/ci/EV000000699", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/28771436", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA16020812/MONDO:0009861/006/0/1651/1653", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA16020812/MONDO:0009861/006/1/1652", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA16020812/MONDO:0009861/006/0/1651", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16020812/MONDO:0009861/006/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16020812/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": "2021/2/12", "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/CA16020812/MONDO:0009861/006/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA16020812/MONDO:0009861/006/ci/CA16020812/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": "c.533A>G (p.Glu178Gly) Pathogenic by 6 submitters", "contributionDate": { "date": "2021/2/12", "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": "CA16020812/MONDO:0009861/006/ci/CA16020812/MONDO:0009861/006.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA16020812/MONDO:0009861/006/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA16020812/MONDO:0009861/006/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA16020812/MONDO:0009861/006/0/1780", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16020812/MONDO:0009861/006/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16020812/MONDO:0009861/006/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "contributionDate": { "date": "2021/2/12", "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/0062", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0062", "label": "PP3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16020812/MONDO:0009861/006/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA16020812/MONDO:0009861/006/ci/CA16020812/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": "SIFT=T, Polyphen2=B, MutationTaster=D. REVEL=0.607", "contributionDate": { "date": "2021/2/12", "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": "CA16020812/MONDO:0009861/006/ci/CA16020812/MONDO:0009861/006.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA16020812/MONDO:0009861/006/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA16020812/MONDO:0009861/006/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA16020812/MONDO:0009861/006/0/1747", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA16020812/MONDO:0009861/006", "metadata": { "created": "2024-09-27T21:34:58.107Z", "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 21:34:58 -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": "c54336ad-7a33-4a07-895c-275c08ab017c", "variant": { "@id": "https://reg.genome.network/allele/CA16020812", "id": "CAR:CA16020812", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000277.3:c.532G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000277.3(PAH):c.532G>A (p.Glu178Lys)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-31T01:17:13.991Z" } }, "status": { "code": 200, "name": "OK" } }