rs398123220
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_000169.3(GLA):c.734G>T(p.Trp245Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000166 in 1,207,088 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000169.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000891 AC: 1AN: 112186Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34344
GnomAD4 exome AF: 9.13e-7 AC: 1AN: 1094902Hom.: 0 Cov.: 30 AF XY: 0.00000278 AC XY: 1AN XY: 360298
GnomAD4 genome AF: 0.00000891 AC: 1AN: 112186Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34344
ClinVar
Submissions by phenotype
Fabry disease Uncertain:2
This missense variant replaces tryptophan with leucine at codon 245 of the GLA protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with GLA-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. -
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not provided Uncertain:2
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at