1-2030028-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000815.5(GABRD):c.1105G>T(p.Gly369Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. G369S) has been classified as Uncertain significance.
Frequency
Consequence
NM_000815.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GABRD | NM_000815.5 | c.1105G>T | p.Gly369Cys | missense_variant | Exon 9 of 9 | ENST00000378585.7 | NP_000806.2 | |
GABRD | XM_017000936.2 | c.1810G>T | p.Gly604Cys | missense_variant | Exon 8 of 8 | XP_016856425.1 | ||
GABRD | XM_011541194.4 | c.1144G>T | p.Gly382Cys | missense_variant | Exon 9 of 9 | XP_011539496.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248292Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135004
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Idiopathic generalized epilepsy Uncertain:1
This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 369 of the GABRD protein (p.Gly369Cys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with GABRD-related conditions. ClinVar contains an entry for this variant (Variation ID: 942297). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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