ClinVar Miner

Submissions for variant NM_000512.5(GALNS):c.758G>A (p.Arg253Gln)

gnomAD frequency: 0.00001  dbSNP: rs769560969
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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 RCV001578394 SCV001547787 uncertain significance 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_supporting); very low frequency in gnomAD v2.1.1 (PM2_moderate)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002307732 SCV002600765 uncertain significance not specified 2022-10-28 criteria provided, single submitter clinical testing Variant summary: GALNS c.758G>A (p.Arg253Gln) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. Several computational tools predict a significant impact on normal splicing: Four predict the variant weakens a 5' donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8e-06 in 251240 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.758G>A has been reported in the literature in the compound heterozygous state in an individual affected with Mucopolysaccharidosis Type IVA (Morquio Syndrome A) (e.g. Dung_2013). This report does not provide unequivocal conclusions about association of the variant with Mucopolysaccharidosis Type IVA (Morquio Syndrome A). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One submitter has provided a clinical-significance assessment for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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