rs114703967
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000512.5(GALNS):c.1376C>T(p.Ala459Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00632 in 1,573,198 control chromosomes in the GnomAD database, including 542 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000512.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0324 AC: 4932AN: 152146Hom.: 256 Cov.: 33
GnomAD3 exomes AF: 0.00912 AC: 1761AN: 193128Hom.: 91 AF XY: 0.00633 AC XY: 660AN XY: 104234
GnomAD4 exome AF: 0.00352 AC: 5008AN: 1420934Hom.: 286 Cov.: 33 AF XY: 0.00301 AC XY: 2120AN XY: 704400
GnomAD4 genome AF: 0.0324 AC: 4940AN: 152264Hom.: 256 Cov.: 33 AF XY: 0.0311 AC XY: 2319AN XY: 74462
ClinVar
Submissions by phenotype
Mucopolysaccharidosis, MPS-IV-A Benign:3
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
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not provided Benign:3
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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not specified Benign:1
Variant summary: The GALNS c.1376C>T (p.Ala459Val) variant involves the alteration of a non-conserved nucleotide and 3/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 2649/218538 control chromosomes (gnomAD), predominantly observed in the African subpopulation at a frequency of 0.119713 (2406/20098). This frequency is about 59 times the estimated maximal expected allele frequency of a pathogenic GALNS variant (0.0020412), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. A publication, Bunge_1997, cites the variant of interest in an affected individual, who was homozygote for a pathogenic GALNS variant, G47R. In addition, multiple clinical diagnostic laboratories classified this variant as likely benign/benign. Taken together, this variant is classified as benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at