X-152168286-T-C
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_000808.4(GABRA3):c.1421A>G(p.Tyr474Cys) 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 Pathogenic (★).
Frequency
Genomes: not found (cov: 23)
Consequence
GABRA3
NM_000808.4 missense
NM_000808.4 missense
Scores
13
3
1
Clinical Significance
Conservation
PhyloP100: 7.96
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 8 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.984
PP5
Variant X-152168286-T-C is Pathogenic according to our data. Variant chrX-152168286-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 985441.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-152168286-T-C is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GABRA3 | NM_000808.4 | c.1421A>G | p.Tyr474Cys | missense_variant | 10/10 | ENST00000370314.9 | NP_000799.1 | |
GABRA3 | XM_006724811.4 | c.*186A>G | 3_prime_UTR_variant | 9/9 | XP_006724874.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GABRA3 | ENST00000370314.9 | c.1421A>G | p.Tyr474Cys | missense_variant | 10/10 | 1 | NM_000808.4 | ENSP00000359337 | P1 | |
GABRA3 | ENST00000535043.1 | c.1421A>G | p.Tyr474Cys | missense_variant | 10/10 | 1 | ENSP00000443527 | P1 | ||
ENST00000453915.1 | n.501+3698T>C | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
Cov.:
23
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome Cov.: 23
GnomAD4 genome
Cov.:
23
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 17, 2018 | - - |
Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 22, 2022 | - - |
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
Uncertain
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
Gain of catalytic residue at W475 (P = 0.032);Gain of catalytic residue at W475 (P = 0.032);
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