ClinVar Miner

Submissions for variant NM_000047.3(ARSL):c.217G>A (p.Gly73Ser)

dbSNP: rs2147394157
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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 RCV002242769 SCV001574195 likely pathogenic Chondrodysplasia punctata, brachytelephalangic, autosomal 2022-12-14 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 73 of the ARSE protein (p.Gly73Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with chondrodysplasia punctata (PMID: 23470839). ClinVar contains an entry for this variant (Variation ID: 1066074). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects ARSE function (PMID: 23470839). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
3billion, Medical Genetics RCV001376980 SCV002058422 likely pathogenic X-linked chondrodysplasia punctata 1 2022-01-03 criteria provided, single submitter clinical testing Same nucleotide change resulting in same amino acid change has been previously reported to be associated with ARSL related disorder (ClinVar ID: VCV001066074, PMID:23470839, PS1_P). The variant has been observed in at least two similarly affected unrelated individuals (PMID: 23470839, PS4_M). Functional studies provide moderate evidence of the variant having a damaging effect on the gene or gene product(PMID: 23470839, PS3_M). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.816, PP3_P). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.

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