X-152168389-G-T

Position:

• chrX-152168389-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000808.4(GABRA3):​c.1318C>A​(p.Gln440Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: GABRA3 NM_000808.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.11

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]

ENSG00000231937 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14876404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA3	NM_000808.4	c.1318C>A	p.Gln440Lys	missense_variant	10/10	ENST00000370314.9	NP_000799.1
GABRA3	XM_006724811.4	c.*83C>A		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.1318C>A	p.Gln440Lys	missense_variant	10/10	1	NM_000808.4	ENSP00000359337.4
GABRA3	ENST00000535043.1	c.1318C>A	p.Gln440Lys	missense_variant	10/10	1		ENSP00000443527.1
ENSG00000231937	ENST00000453915.1	n.501+3801G>T		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2024

GABRA3: PM2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	22
DANN	Benign	0.92
DEOGEN2	Benign	0.19	T;T
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.70	.;T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.38	N;N
REVEL	Benign	0.20
Sift	Benign	0.15	T;T
Sift4G	Benign	0.46	T;T
Polyphen		0.0	B;B
Vest4		0.054
MutPred		0.38		Gain of ubiquitination at Q440 (P = 0.006);Gain of ubiquitination at Q440 (P = 0.006);
MVP		0.88
MPC		0.46
ClinPred		0.18	T
GERP RS		3.6
Varity_R		0.19
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-151336861;