ClinVar Miner

Submissions for variant NM_000046.5(ARSB):c.478C>T (p.Arg160Ter)

gnomAD frequency: 0.00002  dbSNP: rs1255777033
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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 RCV000656129 SCV000609483 pathogenic Mucopolysaccharidosis type 6 2015-12-01 criteria provided, single submitter research
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV000656129 SCV000803083 pathogenic Mucopolysaccharidosis type 6 2018-01-01 criteria provided, single submitter curation Nonsense variant (PVS1); 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 ExAC (PM2)
Invitae RCV000656129 SCV002240372 pathogenic Mucopolysaccharidosis type 6 2023-12-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg160*) in the ARSB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ARSB are known to be pathogenic (PMID: 17458871, 22133300). This variant is present in population databases (no rsID available, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with ARSB-related conditions (PMID: 8125475, 33163362). ClinVar contains an entry for this variant (Variation ID: 445291). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000656129 SCV002511470 pathogenic Mucopolysaccharidosis type 6 2022-04-11 criteria provided, single submitter clinical testing Variant summary: ARSB c.478C>T (p.Arg160X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 251472 control chromosomes. c.478C>T has been reported in the literature in individuals affected with Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome) (example, Garrido_2007, Jurecka_2012). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics RCV000656129 SCV004209069 pathogenic Mucopolysaccharidosis type 6 2023-09-16 criteria provided, single submitter clinical testing

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