ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.902G>A (p.Arg301Gln)

gnomAD frequency: 0.00003  dbSNP: rs573456864
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000688435 SCV000816045 uncertain significance Metachromatic leukodystrophy 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 301 of the ARSA protein (p.Arg301Gln). This variant is present in population databases (rs573456864, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ARSA-related conditions. ClinVar contains an entry for this variant (Variation ID: 568168). 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 ARSA protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts the p.Arg301 amino acid residue in ARSA. Other variant(s) that disrupt this residue have been observed in individuals with ARSA-related conditions (PMID: 12809637, 30674982), which suggests that this may be a clinically significant amino acid residue. 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.
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000688435 SCV002754483 uncertain significance Metachromatic leukodystrophy criteria provided, single submitter clinical testing A Heterozygous missense variation in exon 5 of the ARSA gene that results in the amino acid substitution of glutamine for Arginine at codon 301 was detected. The observed variant c.902G>A (p.Arg301Gln) has not been reported in the 1000 genomes and has MAF of 0.003% in gnomAD databases. The in silico prediction of the variant are possibly damaging by MutationTaster2. The reference codon is conserved across species.In summary, the variant meets our criteria to be classified as a variant of uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV000688435 SCV002780714 uncertain significance Metachromatic leukodystrophy 2022-04-13 criteria provided, single submitter clinical testing
Natera, Inc. RCV000688435 SCV002081652 uncertain significance Metachromatic leukodystrophy 2019-10-28 no assertion criteria provided clinical testing

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