ClinVar Miner

Submissions for variant NM_000512.5(GALNS):c.289T>G (p.Phe97Val)

dbSNP: rs2143005083
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Total submissions: 2
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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 RCV001578283 SCV001547651 uncertain significance Mucopolysaccharidosis, MPS-IV-A 2021-02-01 criteria provided, single submitter curation Absent from 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 RCV001578283 SCV004296421 likely pathogenic Mucopolysaccharidosis, MPS-IV-A 2022-12-31 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects GALNS function (PMID: 8826435, 9375852, 10814710). 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: 1048180). This missense change has been observed in individual(s) with mucopolysaccharidosis type IVA (PMID: 8826435). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 97 of the GALNS protein (p.Phe97Val).

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