{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/b3e35b5f-86ea-4be0-804a-8a98e4125fde/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1537428517", "label": "ClinGen Peroxisomal Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ABCD1 Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0018544", "id": "MONDO:0018544", "label": "adrenoleukodystrophy", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA278414/MONDO:0018544/105/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA278414/MONDO:0018544/105/ei/1/1697", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822", "id": "CG-PCER-AGENT:CG_50049_EP177618055787822", "type": "Agent" }, "contributionDate": { "date": "2026/4/15", "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/CA278414/MONDO:0018544/105/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA278414/MONDO:0018544/105/ci/CA278414/MONDO:0018544/105.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822", "id": "CG-PCER-AGENT:CG_50049_EP177618055787822", "type": "Agent" }, "comments": "Authors in PMID: 17542813 introduced the c.346G>A (p.Gly116Arg) variant into X-ALD fibroblasts as transiently expressed mutant His-ALDP as well as CHO-K1 cells stably expressing both wild type ALDP and mutant ALDP-green fluorescence proteins (GFPs). Gly116Arg is shown to be localized to the peroxisome with punctate staining on immunofluorescence assay in both ALD fibroblasts (and CHO cells with data not shown). However, β-oxidation activity was not restored by the transfection of the mutant cDNA (Fig 3A suggests activity was ~50% of that of WT), although a substantial amount of mutant ALDPs was expressed in the cells. PS3_Supporting is applied at this time, until more evidence to increase PS3 strength can be generated.", "contributionDate": { "date": "2026/4/15", "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": "CA278414/MONDO:0018544/105/ci/CA278414/MONDO:0018544/105.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA278414/MONDO:0018544/105/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA278414/MONDO:0018544/105/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA278414/MONDO:0018544/105/0/1696", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA278414/MONDO:0018544/105/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA278414/MONDO:0018544/105/ei/1/1832", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822", "id": "CG-PCER-AGENT:CG_50049_EP177618055787822", "type": "Agent" }, "contributionDate": { "date": "2026/4/15", "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/CA278414/MONDO:0018544/105/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA278414/MONDO:0018544/105/ci/CA278414/MONDO:0018544/105.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822", "id": "CG-PCER-AGENT:CG_50049_EP177618055787822", "type": "Agent" }, "comments": "One female newborn proband is reported in PMID: 35466195 with the c.346G>A (p.Gly116Arg) variant detected by NGS (Table 1). Proband was studied based on elevated C26:0-lysoPC on repeat samples and increased VLCFA C26:0 on dried blood spots. Proband's mother is also noted to be heterozygous for the variant, and a positive family history is noted, wherein family members with confirmed, symptomatic X-ALD phenotype were present. Proband meets PP4_Moderate.", "contributionDate": { "date": "2026/4/15", "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": "CA278414/MONDO:0018544/105/ci/CA278414/MONDO:0018544/105.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA278414/MONDO:0018544/105/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA278414/MONDO:0018544/105/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA278414/MONDO:0018544/105/0/1831", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA278414/MONDO:0018544/105/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA278414/MONDO:0018544/105/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822", "id": "CG-PCER-AGENT:CG_50049_EP177618055787822", "type": "Agent" }, "contributionDate": { "date": "2026/4/15", "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/CA278414/MONDO:0018544/105/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA278414/MONDO:0018544/105/ci/CA278414/MONDO:0018544/105.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822", "id": "CG-PCER-AGENT:CG_50049_EP177618055787822", "type": "Agent" }, "comments": "This missense variant has a REVEL score of 0.974, which is above the PP3 threshold (>=0.85) for ABCD1 set by the Peroxisomal VCEP (PP3).", "contributionDate": { "date": "2026/4/15", "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": "CA278414/MONDO:0018544/105/ci/CA278414/MONDO:0018544/105.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA278414/MONDO:0018544/105/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA278414/MONDO:0018544/105/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA278414/MONDO:0018544/105/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA278414/MONDO:0018544/105/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA278414/MONDO:0018544/105/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822", "id": "CG-PCER-AGENT:CG_50049_EP177618055787822", "type": "Agent" }, "contributionDate": { "date": "2026/4/15", "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/CA278414/MONDO:0018544/105/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA278414/MONDO:0018544/105/ci/CA278414/MONDO:0018544/105.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822", "id": "CG-PCER-AGENT:CG_50049_EP177618055787822", "type": "Agent" }, "comments": "The c.346G>A (p.Gly116Arg) variant is completely absent from gnomAD v2.1.1, v3.1.2. and v4", "contributionDate": { "date": "2026/4/15", "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": "CA278414/MONDO:0018544/105/ci/CA278414/MONDO:0018544/105.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA278414/MONDO:0018544/105/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA278414/MONDO:0018544/105/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA278414/MONDO:0018544/105/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA278414/MONDO:0018544/105/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA278414/MONDO:0018544/105/ei/1/1736", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822", "id": "CG-PCER-AGENT:CG_50049_EP177618055787822", "type": "Agent" }, "contributionDate": { "date": "2026/4/15", "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/CA278414/MONDO:0018544/105/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA278414/MONDO:0018544/105/ci/CA278414/MONDO:0018544/105.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822", "id": "CG-PCER-AGENT:CG_50049_EP177618055787822", "type": "Agent" }, "comments": "With 5 probands reported in the literature, each meeting at least supporting criteria for phenotype codes, PS4 is met at the strong level.", "contributionDate": { "date": "2026/4/15", "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": "CA278414/MONDO:0018544/105/ci/CA278414/MONDO:0018544/105.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA278414/MONDO:0018544/105/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA278414/MONDO:0018544/105/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA278414/MONDO:0018544/105/0/1735", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA278414/MONDO:0018544/105", "metadata": { "created": "2026-04-15T15:33:34.139Z", "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, 15 Apr 2026 15:33:33 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "b3e35b5f-86ea-4be0-804a-8a98e4125fde", "variant": { "@id": "https://reg.genome.network/allele/CA278414", "id": "CAR:CA278414", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000033.4:c.346G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000033.4(ABCD1):c.346G>A (p.Gly116Arg)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-31T07:38:14.204Z" } }, "status": { "code": 200, "name": "OK" } }