ClinVar Miner

Submissions for variant NM_000512.5(GALNS):c.489del (p.Asn164fs) (rs1328983959)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000796738 SCV000936263 pathogenic Mucopolysaccharidosis, MPS-IV-A 2018-08-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn164Thrfs*35) in the GALNS gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with mucopolysaccharidosis type IVa (PMID: 9298823). Loss-of-function variants in GALNS are known to be pathogenic (PMID: 12442278). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193734 SCV001362796 likely pathogenic Morquio syndrome 2019-01-24 criteria provided, single submitter clinical testing Variant summary: The variant, GALNS c.489delC (p.Asn164ThrfsX35) 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 nearby of this position have been classified as pathogenic by our laboratory (eg. c.498delC (p.Phe167fsX32)). The variant allele was found at a frequency of 4.1e-06 in 246236 control chromosomes (gnomAD) and has been reported in the literature in individuals affected with Mucopolysaccharidosis Type IVA (Morquio Syndrome A, Bunge_1997). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Laboratory of Diagnosis and Therapy of Lysosomal Disorders,University of Padova RCV000796738 SCV001547714 pathogenic Mucopolysaccharidosis, MPS-IV-A 2021-02-01 criteria provided, single submitter research Frameshift variant (PVS1_very strong); the prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (PS4_strong); absent from gnomAD v2.1.1 (PM2_moderate)

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