Submissions for variant NM_000512.5(GALNS):c.1387G>T (p.Glu463Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Neuberg Centre For Genomic Medicine, NCGM	RCV003388659	SCV004100351	likely pathogenic	Mucopolysaccharidosis, MPS-IV-A		criteria provided, single submitter	clinical testing	The stop gained p.E463* in GALNS (NM_000512.5) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.E463* variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant is predicted to cause loss of normal protein function through protein truncation. The p.E463* variant is a loss of function variant in the gene GALNS, which is intolerant of Loss of Function variants. For these reasons, this variant has been classified as Likely Pathogenic.
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	RCV003388659	SCV004174850	likely pathogenic	Mucopolysaccharidosis, MPS-IV-A	2023-12-08	criteria provided, single submitter	clinical testing	A homozygous nonsense variation in exon 13 of the GALNS gene that results in a stop codon and premature truncation of the protein at codon 463 was detected. The observed variant c.1387G>T (p.Glu463Ter) has not been reported in 1000 genomes and gnomAD databases. The in-silico prediction of the variant is disease causing by MutationTaster2 and DANN. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as a likely pathogenic.