chr16-88824832-C-A
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1
The NM_000512.5(GALNS):c.1177G>T(p.Ala393Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0521 in 1,613,270 control chromosomes in the GnomAD database, including 2,482 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 -18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0535 AC: 8146AN: 152184Hom.: 256 Cov.: 33
GnomAD3 exomes AF: 0.0617 AC: 15403AN: 249724Hom.: 529 AF XY: 0.0635 AC XY: 8594AN XY: 135442
GnomAD4 exome AF: 0.0520 AC: 75920AN: 1460968Hom.: 2225 Cov.: 32 AF XY: 0.0530 AC XY: 38486AN XY: 726746
GnomAD4 genome AF: 0.0536 AC: 8165AN: 152302Hom.: 257 Cov.: 33 AF XY: 0.0553 AC XY: 4118AN XY: 74466
ClinVar
Submissions by phenotype
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_stand-alone); 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) -
not specified Benign:3
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Variant summary: GALNS c.1177G>T (p.Ala393Ser) results in a conservative amino acid change located in the Sulfatase, N-terminal domain of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.06 in 275882 control chromosomes in the gnomAD database, including 553 homozygotes. The observed variant frequency is approximately 29-folds higher than 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. Three ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as benign. -
not provided Benign:3
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This variant is associated with the following publications: (PMID: 25252036, 24035930, 16837223, 21251309, 15235041, 15241807, 9452036) -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at