X-152168391-A-G

Position:

• chrX-152168391-A-G

Variant summary

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

The ENST00000370314.9(GABRA3):​c.1316T>C​(p.Val439Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 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 ENST00000370314.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21

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]

(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=0.08383247).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA3	NM_000808.4	c.1316T>C	p.Val439Ala	missense_variant	10/10	ENST00000370314.9	NP_000799.1
GABRA3	XM_006724811.4	c.*81T>C		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.1316T>C	p.Val439Ala	missense_variant	10/10	1	NM_000808.4	ENSP00000359337	P1
GABRA3	ENST00000535043.1	c.1316T>C	p.Val439Ala	missense_variant	10/10	1		ENSP00000443527	P1
	ENST00000453915.1	n.501+3803A>G		intron_variant, non_coding_transcript_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

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2024

The c.1316T>C (p.V439A) alteration is located in exon 10 (coding exon 9) of the GABRA3 gene. This alteration results from a T to C substitution at nucleotide position 1316, causing the valine (V) at amino acid position 439 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.78
DEOGEN2	Benign	0.20	T;T
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.67	.;T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.084	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.69	N;N
MutationTaster	Benign	0.98	N;N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.64	N;N
REVEL	Benign	0.18
Sift	Benign	0.77	T;T
Sift4G	Benign	0.51	T;T
Polyphen		0.0040	B;B
Vest4		0.038
MutPred		0.23		Gain of glycosylation at S442 (P = 0.1029);Gain of glycosylation at S442 (P = 0.1029);
MVP		0.88
MPC		0.46
ClinPred		0.13	T
GERP RS		4.6
Varity_R		0.091
gMVP		0.38

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-151336863;