ClinVar Miner

Submissions for variant NM_004035.7(ACOX1):c.176G>C (p.Arg59Pro)

gnomAD frequency: 0.00001  dbSNP: rs777937235
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
UCLA Clinical Genomics Center, UCLA RCV000196696 SCV000255316 likely pathogenic Acyl-CoA oxidase deficiency 2014-02-18 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000196696 SCV003483323 uncertain significance Acyl-CoA oxidase deficiency 2023-08-10 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with peroxisomal acyl-CoA oxidase deficiency (PMID: 25326637). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 59 of the ACOX1 protein (p.Arg59Pro). This variant is present in population databases (rs777937235, gnomAD 0.006%). ClinVar contains an entry for this variant (Variation ID: 216884). 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 ACOX1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004526641 SCV005040641 uncertain significance not specified 2024-03-27 criteria provided, single submitter clinical testing Variant summary: ACOX1 c.176G>C (p.Arg59Pro) results in a non-conservative amino acid change located in the Acyl-coenzyme A oxidase, N-terminal (IPR029320) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251494 control chromosomes. c.176G>C has been reported in the literature in individuals affected with Pseudoneonatal Adrenoleukodystrophy (Lee_2014). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 25326637). ClinVar contains an entry for this variant (Variation ID: 216884). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

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