ClinVar Miner

Submissions for variant NM_000046.5(ARSB):c.160G>A (p.Asp54Asn)

dbSNP: rs1554032216
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV000677505 SCV000803015 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); Located in a well-established functional domain (PM1); Absent from GnomAD (PM2); Multiple lines of computational evidence support a deleterious effect on the gene product (PP3)
Labcorp Genetics (formerly Invitae), Labcorp RCV000677505 SCV002245562 pathogenic Mucopolysaccharidosis type 6 2023-11-09 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 54 of the ARSB protein (p.Asp54Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 17458871, 24243352, 26609033). ClinVar contains an entry for this variant (Variation ID: 559730). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects ARSB function (PMID: 27826022). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV004719941 SCV005325519 pathogenic not provided 2023-09-08 criteria provided, single submitter clinical testing Expression studies found D54N is associated with a decrease in enzyme activity similar to that caused by loss of function variants in this gene (Uttarilli et al., 2017); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 17458871, 27826022, 26609033)

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