NM_000512.5:c.199C>A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000512.5(GALNS):c.199C>A(p.Leu67Met) variant causes a missense change. The variant allele was found at a frequency of 0.0179 in 1,612,930 control chromosomes in the GnomAD database, including 4,252 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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: 0.0931 AC: 14157AN: 152132Hom.: 2175 Cov.: 33
GnomAD3 exomes AF: 0.0243 AC: 6022AN: 247650Hom.: 829 AF XY: 0.0178 AC XY: 2395AN XY: 134356
GnomAD4 exome AF: 0.0100 AC: 14616AN: 1460680Hom.: 2070 Cov.: 33 AF XY: 0.00874 AC XY: 6351AN XY: 726564
GnomAD4 genome AF: 0.0932 AC: 14190AN: 152250Hom.: 2182 Cov.: 33 AF XY: 0.0890 AC XY: 6624AN XY: 74446
ClinVar
Submissions by phenotype
not specified Benign:5
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Variant summary: The GALNS c.199C>A (p.Leu67Met) variant located in the Sulfatase, N-terminal (InterPro) involves the alteration of a conserved nucleotide and 5/5 in silico tools predict a benign outcome for this variant. This variant was found in 8588/274128 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.327481 (7722/23580). This frequency is about 160 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, Laradi_2006 found the variant of interest to co-occur with pathogenic GALNS variants. In addition, multiple clinical diagnostic laboratories classified this variant as benign. Taken together, this variant is classified as benign. -
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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. -
Mucopolysaccharidosis, MPS-IV-A Benign:4
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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Allele frequency is >5% in gnomAD v2.1.1 (BA1); allele frequency is greater than expected for disorder (BS1_strong); multiple lines of computational evidence suggest no impact on gene or gene product (BP4_supporting) -
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not provided Benign:3
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at