rs910130675
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP2PP3
The NM_003042.4(SLC6A1):c.1255C>T(p.Arg419Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,612,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. R419H) has been classified as Benign.
Frequency
Consequence
NM_003042.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC6A1 | NM_003042.4 | c.1255C>T | p.Arg419Cys | missense_variant | 12/16 | ENST00000287766.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC6A1 | ENST00000287766.10 | c.1255C>T | p.Arg419Cys | missense_variant | 12/16 | 1 | NM_003042.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249158Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134560
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1460734Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12AN XY: 726534
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74344
ClinVar
Submissions by phenotype
Myoclonic-atonic epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 12, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 419 of the SLC6A1 protein (p.Arg419Cys). This variant is present in population databases (no rsID available, gnomAD 0.03%). This missense change has been observed in individual(s) with seizures (PMID: 35761184). ClinVar contains an entry for this variant (Variation ID: 542202). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SLC6A1 protein function with a negative predictive value of 80%. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at