chrX-152168449-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_000808.4(GABRA3):c.1258G>A(p.Ala420Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000463 in 1,209,507 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes in GnomAD. 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000046 ( 0 hom. 18 hem. )

Consequence

GABRA3
NM_000808.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.99

Variant links:

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]

GABRA3 links:

ENSG00000231937 (HGNC:):

ENSG00000231937 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.22615841).

BP6

Variant X-152168449-C-T is Benign according to our data. Variant chrX-152168449-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2673264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAdExome4 at 18 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA3	NM_000808.4 link	c.1258G>A	p.Ala420Thr	missense_variant	Exon 10 of 10	ENST00000370314.9	NP_000799.1	P34903
GABRA3	XM_006724811.4 link	c.*23G>A		3_prime_UTR_variant	Exon 9 of 9		XP_006724874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GABRA3	ENST00000370314.9 link	c.1258G>A	p.Ala420Thr	missense_variant	Exon 10 of 10	1	NM_000808.4	ENSP00000359337.4	P34903
GABRA3	ENST00000535043.1 link	c.1258G>A	p.Ala420Thr	missense_variant	Exon 10 of 10	1		ENSP00000443527.1	P34903
ENSG00000231937	ENST00000453915.1 link	n.501+3861C>T		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.0000447

AC:

AN:

111966

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34112

show subpopulations

Gnomad AFR

AF:

0.000130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000273

AC:

AN:

183444

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

67890

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000244

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000465

AC:

AN:

1097541

Hom.:

Cov.:

AF XY:

0.0000496

AC XY:

AN XY:

362917

show subpopulations

Gnomad4 AFR exome

AF:

0.000190

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000259

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000368

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000447

AC:

AN:

111966

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34112

show subpopulations

Gnomad4 AFR

AF:

0.000130

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features

Benign:1

Mar 29, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Nov 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

GABRA3: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.19

T;T

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.63

.;T

M_CAP

Benign

0.063

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-0.58

MutationAssessor

Benign

1.1

L;L

PrimateAI

Benign

0.47

PROVEAN

Benign

0.22

N;N

REVEL

Benign

0.27

Sift

Benign

0.21

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.98

D;D

Vest4

0.17

MutPred

0.27

Loss of catalytic residue at A420 (P = 0.0168);Loss of catalytic residue at A420 (P = 0.0168);

MVP

0.94

MPC

0.61

ClinPred

0.13

GERP RS

3.9

Varity_R

0.059

gMVP

0.34

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over