ClinVar Miner

Submissions for variant NM_000512.5(GALNS):c.485C>T (p.Ser162Phe)

gnomAD frequency: 0.00001  dbSNP: rs118204444
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000723452 SCV000700409 pathogenic not provided 2017-03-07 criteria provided, single submitter clinical testing
Invitae RCV000000744 SCV000829947 pathogenic Mucopolysaccharidosis, MPS-IV-A 2023-11-13 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 162 of the GALNS protein (p.Ser162Phe). This variant is present in population databases (rs118204444, gnomAD 0.003%). This missense change has been observed in individuals with mucopolysaccharidosis type IVA (PMID: 9385378, 23876334, 29731656). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 709). 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: 10814710). For these reasons, this variant has been classified as Pathogenic.
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV000000744 SCV001547712 pathogenic Mucopolysaccharidosis, MPS-IV-A 2021-02-01 criteria provided, single submitter research In vivo and in vitro functional studies supportive of a damaging effect on the gene product (low to null enzymatic activity in homozygotes; low to null in vitro enzymatic activity; PS3_strong); 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)
Genome-Nilou Lab RCV000000744 SCV002045023 pathogenic Mucopolysaccharidosis, MPS-IV-A 2021-11-07 criteria provided, single submitter clinical testing
OMIM RCV000000744 SCV000020894 pathogenic Mucopolysaccharidosis, MPS-IV-A 1997-11-01 no assertion criteria provided literature only

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