ClinVar Miner

Submissions for variant NM_000512.5(GALNS):c.178G>A (p.Asp60Asn)

gnomAD frequency: 0.00003  dbSNP: rs118204447
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Total submissions: 4
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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 RCV000000749 SCV001547610 likely pathogenic Mucopolysaccharidosis, MPS-IV-A 2021-02-01 criteria provided, single submitter curation The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (PS4_strong); very low frequency in gnomAD v2.1.1 (PM2_moderate); multiple lines of computational evidence support a deleterious effect on the gene (PP3_supporting)
Labcorp Genetics (formerly Invitae), Labcorp RCV000000749 SCV004296425 pathogenic Mucopolysaccharidosis, MPS-IV-A 2023-12-11 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 60 of the GALNS protein (p.Asp60Asn). This variant is present in population databases (rs118204447, gnomAD 0.004%). This missense change has been observed in individuals with mucopolysaccharidosis type IVA (PMID: 9298823, 12721840). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 714). 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 GALNS protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects GALNS function (PMID: 12721840). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000000749 SCV000020899 pathogenic Mucopolysaccharidosis, MPS-IV-A 2003-07-01 no assertion criteria provided literature only
GeneReviews RCV000000749 SCV001761894 not provided Mucopolysaccharidosis, MPS-IV-A no assertion provided literature only

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