rs138085358
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS2
The NM_004172.5(SLC1A3):c.1496G>A(p.Arg499Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000123 in 1,614,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004172.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC1A3 | NM_004172.5 | c.1496G>A | p.Arg499Gln | missense_variant | Exon 10 of 10 | ENST00000265113.9 | NP_004163.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152166Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000795 AC: 20AN: 251472Hom.: 0 AF XY: 0.0000956 AC XY: 13AN XY: 135916
GnomAD4 exome AF: 0.000129 AC: 189AN: 1461840Hom.: 0 Cov.: 32 AF XY: 0.000122 AC XY: 89AN XY: 727230
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152284Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5AN XY: 74472
ClinVar
Submissions by phenotype
Episodic ataxia type 6 Pathogenic:1Uncertain:2
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not provided Uncertain:2Benign:1
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 499 of the SLC1A3 protein (p.Arg499Gln). This variant is present in population databases (rs138085358, gnomAD 0.01%). This missense change has been observed in individual(s) with ataxia (PMID: 25497598). This variant is also known as Arg454Gln. ClinVar contains an entry for this variant (Variation ID: 242994). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt SLC1A3 protein function with a negative predictive value of 80%. Studies have shown that this missense change alters SLC1A3 gene expression (PMID: 32741053). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
SLC1A3: BS1 -
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not specified Uncertain:1Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at