ClinVar Miner

Submissions for variant NM_000512.5(GALNS):c.1164C>A (p.Asp388Glu)

gnomAD frequency: 0.00001  dbSNP: rs752339162
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000633460 SCV000754689 pathogenic Mucopolysaccharidosis, MPS-IV-A 2023-03-13 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GALNS protein function. ClinVar contains an entry for this variant (Variation ID: 528322). This missense change has been observed in individual(s) with mucopolysaccharidosis type IVA (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 (rs752339162, gnomAD 0.003%). This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 388 of the GALNS protein (p.Asp388Glu).
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV000633460 SCV001547911 uncertain significance 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_moderate); very low frequency in gnomAD v2.1.1 (PM2_moderate); multiple lines of computational evidence suggest no impact on gene or gene product (BP4_supporting)
Genome-Nilou Lab RCV000633460 SCV002044939 uncertain significance Mucopolysaccharidosis, MPS-IV-A 2021-11-07 criteria provided, single submitter clinical testing

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