ClinVar Miner

Submissions for variant NM_001611.5(ACP5):c.781G>T (p.Gly261Trp)

dbSNP: rs2145082191
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002030751 SCV002272259 uncertain significance Spondyloenchondrodysplasia with immune dysregulation 2024-07-08 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 261 of the ACP5 protein (p.Gly261Trp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ACP5-related conditions. ClinVar contains an entry for this variant (Variation ID: 1486814). 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 ACP5 protein function with a positive predictive value of 80%. 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.
Neuberg Centre For Genomic Medicine, NCGM RCV002030751 SCV004048198 uncertain significance Spondyloenchondrodysplasia with immune dysregulation criteria provided, single submitter clinical testing The missense variant c.781G>T (p.Gly261Trp) in ACP5 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Gly261Trp variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. The amino acid Gly at position 261 is changed to a Trp changing protein sequence and it might alter its composition and physico-chemical properties. This variant has not been reported to the ClinVar database. The variant is predicted to be damaging by both SIFT and PolyPhen2. The residue is conserved across species. The amino acid change p.Gly261Trp in ACP5 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS).

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