Variant X-152256002-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000808.4(GABRA3):c.331-4C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000394 in 1,168,858 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 165 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., 8 hem., cov: 23)

Exomes 𝑓: 0.00041 ( 0 hom. 157 hem. )

Consequence

GABRA3
NM_000808.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002727

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.209

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant X-152256002-G-A is Benign according to our data. Variant chrX-152256002-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 742959.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA3	NM_000808.4 linkuse as main transcript	c.331-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000370314.9	NP_000799.1
GABRA3	XM_006724811.4 linkuse as main transcript	c.331-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			XP_006724874.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
GABRA3	ENST00000370314.9 linkuse as main transcript	c.331-4C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_000808.4	ENSP00000359337	P1
GABRA3	ENST00000535043.1 linkuse as main transcript	c.331-4C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000443527	P1
GABRA3	ENST00000417858.1 linkuse as main transcript		upstream_gene_variant	3

Frequencies

GnomAD3 genomes

AF:

0.000259

AC:

AN:

100496

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

AN XY:

26968

show subpopulations

Gnomad AFR

AF:

0.0000425

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000200

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:

0.000431

Gnomad OTH

AF:

0.000719

GnomAD3 exomes

AF:

0.000192

AC:

AN:

177503

Hom.:

AF XY:

0.000239

AC XY:

AN XY:

62881

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000165

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000376

Gnomad OTH exome

AF:

0.000229

GnomAD4 exome

AF:

0.000407

AC:

435

AN:

1068362

Hom.:

Cov.:

AF XY:

0.000467

AC XY:

157

AN XY:

336118

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000285

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000131

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000500

Gnomad4 OTH exome

AF:

0.000421

GnomAD4 genome

AF:

0.000259

AC:

AN:

100496

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

AN XY:

26968

show subpopulations

Gnomad4 AFR

AF:

0.0000425

Gnomad4 AMR

AF:

0.000200

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000431

Gnomad4 OTH

AF:

0.000719

Alfa

AF:

0.000477

Hom.:

Bravo

AF:

0.000185

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

GABRA3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 28, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.5

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000027

dbscSNV1_RF

Benign

0.0060

SpliceAI score (max)

0.090

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