rs869312155
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_000169.3(GLA):c.926C>T(p.Ala309Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000183 in 1,095,839 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A309G) has been classified as Uncertain significance.
Frequency
Consequence
NM_000169.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLA | NM_000169.3 | c.926C>T | p.Ala309Val | missense_variant | 6/7 | ENST00000218516.4 | |
RPL36A-HNRNPH2 | NM_001199973.2 | c.300+2986G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLA | ENST00000218516.4 | c.926C>T | p.Ala309Val | missense_variant | 6/7 | 1 | NM_000169.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD4 exome AF: 0.00000183 AC: 2AN: 1095839Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 361259
GnomAD4 genome ? Cov.: 23
ClinVar
Submissions by phenotype
Fabry disease Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Uncertain significance, no assertion criteria provided | research | Albrecht-Kossel-Institute, Medical University Rostock | Jan 01, 2014 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 15, 2020 | - - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 18, 2016 | A variant of uncertain significance has been identified in the GLA gene. While the A309V variant has not been published in association with cardiomyopathy, it has been reported in a patient undergoing testing for Fabry disease (Lukas et al., 2016). However, functional studies show that cells expressing this variant have approximately 50% enzyme activity when compared to wild type cells which is consistent with a mild form of Fabry disease (Lukas et al., 2016). The A309V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved across species and where Valine is the wild type in one non-mammalian species. In silico analysis suggests this variant likely does not alter the protein structure/function. Nevertheless, the A309V was not observed in the Exome Aggregation Consortium.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. - |
Uncertain significance, criteria provided, single submitter | research | Gharavi Laboratory, Columbia University | Sep 16, 2018 | - - |
Migalastat response Other:1
drug response, no assertion criteria provided | research | Albrecht-Kossel-Institute, Medical University Rostock | Jan 01, 2014 | - Pharmacological Chaperone response: no |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at