ClinVar Miner

Submissions for variant NM_000512.5(GALNS):c.634-19G>A

gnomAD frequency: 0.20916  dbSNP: rs12934499
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000079039 SCV000110908 benign not specified 2017-11-06 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV000079039 SCV000304615 benign not specified criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000079039 SCV001361772 benign not specified 2019-04-05 criteria provided, single submitter clinical testing Variant summary: GALNS c.634-19G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.27 in 276630 control chromosomes in the gnomAD database, including 11195 homozygotes. The observed variant frequency is approximately 130 fold of the estimated maximal expected allele frequency for a pathogenic variant in GALNS causing Mucopolysaccharidosis Type IVA (Morquio Syndrome A) phenotype (0.002), strongly suggesting that the variant is benign. c.634-19G>A has been reported in the literature in individuals affected with Mucopolysaccharidosis Type IVA (Morquio Syndrome A) in whom other causative variants were identified in homozygous and compound heterozygous states. These data further support a benign outcome due to the presence of this variant in cis with a pathogenic variant. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV001518289 SCV001726957 benign Mucopolysaccharidosis, MPS-IV-A 2024-02-01 criteria provided, single submitter clinical testing
GeneDx RCV000675543 SCV001903509 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001518289 SCV001933717 benign Mucopolysaccharidosis, MPS-IV-A 2021-08-10 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000675543 SCV000801234 benign not provided 2015-10-23 no assertion criteria provided clinical testing

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