15-26547888-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_000814.6(GABRB3):c.1327A>T(p.Thr443Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 151,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. T443T) has been classified as Likely benign.
Frequency
Consequence
NM_000814.6 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 |
---|---|---|---|---|---|---|---|
GABRB3 | NM_000814.6 | c.1327A>T | p.Thr443Ser | missense_variant | 9/9 | ENST00000311550.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABRB3 | ENST00000311550.10 | c.1327A>T | p.Thr443Ser | missense_variant | 9/9 | 1 | NM_000814.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151996Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151996Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74246
ClinVar
Submissions by phenotype
Epilepsy, childhood absence, susceptibility to, 1;C2677087:Epilepsy, childhood absence, susceptibility to, 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 20, 2022 | 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. 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 GABRB3 protein function. This variant has not been reported in the literature in individuals affected with GABRB3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 443 of the GABRB3 protein (p.Thr443Ser). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 10, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at