ClinVar Miner

Submissions for variant NM_000033.4(ABCD1):c.524T>A (p.Phe175Tyr)

dbSNP: rs1569540700
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000755765 SCV000883319 uncertain significance not provided 2017-10-04 criteria provided, single submitter clinical testing The ABCD1 c.524T>A;p.Phe175Tyr variant is not published in the medical literature, in gene-specific databases, or in the ClinVar database. The variant is not listed in the dbSNP variant database or in the general population-based databases. The phenylalanine at this position is highly conserved across species and computational algorithms (Polphen2, SIFT) predict this variant is deleterious. Additionally, this variant occurs in an intracellular loop domain and although the function of this domain is currently unknown, several variants in this region are described in X-linked adrenoleukodystrophy patients (Andreoletti 2017). However, due to insufficient evidence, the clinical significance of this variant cannot be determined with certainty. References: Andreoletti P et al. Predictive Structure and Topology of Peroxisomal ATP-Binding Cassette (ABC) Transporters. Int J Mol Sci. 2017 Jul 22;18(7).
Labcorp Genetics (formerly Invitae), Labcorp RCV001339930 SCV001533707 pathogenic Adrenoleukodystrophy 2023-03-10 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with clinical features of X-linked adrenoleukodystrophy (Invitae). It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ABCD1 protein function. ClinVar contains an entry for this variant (Variation ID: 617946). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with tyrosine, which is neutral and polar, at codon 175 of the ABCD1 protein (p.Phe175Tyr).
Genome-Nilou Lab RCV001339930 SCV002045785 uncertain significance Adrenoleukodystrophy 2021-11-07 criteria provided, single submitter clinical testing

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