ClinVar Miner

Submissions for variant NM_000512.5(GALNS):c.502G>A (p.Gly168Arg)

gnomAD frequency: 0.00001  dbSNP: rs775732598
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000633457 SCV000754686 pathogenic Mucopolysaccharidosis, MPS-IV-A 2022-09-22 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. ClinVar contains an entry for this variant (Variation ID: 528319). This missense change has been observed in individual(s) with mucopolysaccharidosis type IVA (PMID: 9298823, 29275451, 30927141; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs775732598, gnomAD 0.01%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 168 of the GALNS protein (p.Gly168Arg).
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV000633457 SCV001547724 likely pathogenic Mucopolysaccharidosis, MPS-IV-A 2021-02-01 criteria provided, single submitter research 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)
Revvity Omics, Revvity RCV000633457 SCV002024158 pathogenic Mucopolysaccharidosis, MPS-IV-A 2021-07-09 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000633457 SCV002045018 likely pathogenic Mucopolysaccharidosis, MPS-IV-A 2021-11-07 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000633457 SCV005641497 likely pathogenic Mucopolysaccharidosis, MPS-IV-A 2024-04-30 criteria provided, single submitter clinical testing

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