ClinVar Miner

Submissions for variant NM_000512.5(GALNS):c.29G>A (p.Trp10Ter)

dbSNP: rs1967945316
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV001543344 SCV001547570 pathogenic Mucopolysaccharidosis, MPS-IV-A 2021-02-01 criteria provided, single submitter research Nonsense variant (PVS1_very strong); in vitro and vivo functional studies supportive of a damaging effect on the gene product (low to null enzymatic activity in homozygotes; RNA studies evidenced exon skipping; no mutant protein detected by Western Blot analysis; PS3_strong); the prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (PS4_strong); absent from gnomAD v2.1.1 (PM2_moderate)
Lifecell International Pvt. Ltd RCV001543344 SCV003914820 pathogenic Mucopolysaccharidosis, MPS-IV-A criteria provided, single submitter clinical testing A Heterozygous Nonsense variant c.29G>A in Exon 1 of the GALNS gene that results in the amino acid substitution p.Trp10* was identified. The observed variant is novel in gnomAD exomes and genomes. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score. Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Pathogenic [Variation ID: 1048248]. The observed variant has been previously reported in patients affected with mucopolysaccharidosis IVA (Zanetti, Alessandra et al., 2021). For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV001543344 SCV001761893 not provided Mucopolysaccharidosis, MPS-IV-A no assertion provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.