chrX-152189917-G-T
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000808.4(GABRA3):c.956C>A(p.Thr319Asn) variant causes a missense change involving the alteration of a conserved nucleotide. 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 (no stars).
Frequency
Genomes: not found (cov: 22)
Consequence
GABRA3
NM_000808.4 missense
NM_000808.4 missense
Scores
14
2
1
Clinical Significance
Conservation
PhyloP100: 9.94
Genes affected
GABRA3 (HGNC:4077): (gamma-aminobutyric acid type A receptor subunit alpha3) GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. At least 16 distinct subunits of GABA-A receptors have been identified. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.952
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GABRA3 | NM_000808.4 | c.956C>A | p.Thr319Asn | missense_variant | 9/10 | ENST00000370314.9 | NP_000799.1 | |
GABRA3 | XM_006724811.4 | c.931+7716C>A | intron_variant | XP_006724874.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GABRA3 | ENST00000370314.9 | c.956C>A | p.Thr319Asn | missense_variant | 9/10 | 1 | NM_000808.4 | ENSP00000359337 | P1 | |
GABRA3 | ENST00000535043.1 | c.956C>A | p.Thr319Asn | missense_variant | 9/10 | 1 | ENSP00000443527 | P1 | ||
GABRA3 | ENST00000497894.1 | n.27C>A | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD3 genomes
Cov.:
22
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome Cov.: 22
GnomAD4 genome
Cov.:
22
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
GABRA3-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 03, 2024 | The GABRA3 c.956C>A variant is predicted to result in the amino acid substitution p.Thr319Asn. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;D
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Loss of glycosylation at T319 (P = 0.0565);Loss of glycosylation at T319 (P = 0.0565);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.