rs116604393
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000815.5(GABRD):āc.1202C>Gā(p.Thr401Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,428,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T401M) has been classified as Likely benign.
Frequency
Consequence
NM_000815.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABRD | NM_000815.5 | c.1202C>G | p.Thr401Arg | missense_variant | 9/9 | ENST00000378585.7 | |
GABRD | XM_017000936.2 | c.1907C>G | p.Thr636Arg | missense_variant | 8/8 | ||
GABRD | XM_011541194.4 | c.1241C>G | p.Thr414Arg | missense_variant | 9/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABRD | ENST00000378585.7 | c.1202C>G | p.Thr401Arg | missense_variant | 9/9 | 1 | NM_000815.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000140 AC: 2AN: 1428196Hom.: 0 Cov.: 32 AF XY: 0.00000141 AC XY: 1AN XY: 706966
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Idiopathic generalized epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 18, 2018 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with GABRD-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with arginine at codon 401 of the GABRD protein (p.Thr401Arg). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and arginine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at