ClinVar Miner

Submissions for variant NM_000046.5(ARSB):c.479G>A (p.Arg160Gln)

dbSNP: rs1196325597
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Medical Molecular Genetics Department, National Research Center RCV000656130 SCV000609484 pathogenic Mucopolysaccharidosis type 6 2015-12-01 criteria provided, single submitter research
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV000656130 SCV000803084 likely pathogenic Mucopolysaccharidosis type 6 2018-01-01 criteria provided, single submitter curation In vitro functional studies supportive of a damaging effect on the gene product (low to no ARSB activity in homozygotes; PS3); Very low frequency in GnomAD (PM2)
Invitae RCV000656130 SCV001586727 pathogenic Mucopolysaccharidosis type 6 2023-05-24 criteria provided, single submitter clinical testing 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 ARSB protein function. ClinVar contains an entry for this variant (Variation ID: 445292). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 160 of the ARSB protein (p.Arg160Gln). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 8125475, 17643332, 22133300, 24677745, 27797586). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000656130 SCV004038262 pathogenic Mucopolysaccharidosis type 6 2023-08-07 criteria provided, single submitter clinical testing Variant summary: ARSB c.479G>A (p.Arg160Gln) results in a conservative amino acid change located in the sulfatase, N-terminal domain (IPR000917) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251478 control chromosomes (gnomAD). c.479G>A has been reported in the literature as a biallelic genotype in multiple individuals affected with Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome) (e.g. Voskoboeva_1994, Garrido_2007, Kantaputra_2014, Fang_2022). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 34813777, 17643332, 22133300, 24677745, 8125475). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic (n=2)/likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics RCV000656130 SCV004209103 pathogenic Mucopolysaccharidosis type 6 2023-09-12 criteria provided, single submitter clinical testing

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