Variant X-152197789-AAG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_000808.4(GABRA3):c.779-6_779-5del variant causes a splice region, splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.0000938 in 1,193,946 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 41 hemizygotes in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.00010 ( 0 hom. 39 hem. )

Consequence

GABRA3
NM_000808.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.74

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 Likely_benign. Variant got -6 ACMG points.

BP6

Variant X-152197789-AAG-A is Benign according to our data. Variant chrX-152197789-AAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 517942.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-152197789-AAG-A is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA3	NM_000808.4 linkuse as main transcript	c.779-6_779-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000370314.9	NP_000799.1
GABRA3	XM_006724811.4 linkuse as main transcript	c.779-6_779-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			XP_006724874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA3	ENST00000370314.9 linkuse as main transcript	c.779-6_779-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000808.4	ENSP00000359337	P1
GABRA3	ENST00000535043.1 linkuse as main transcript	c.779-6_779-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000443527	P1

Frequencies

GnomAD3 genomes

AF:

0.0000357

AC:

AN:

111953

Hom.:

Cov.:

AF XY:

0.0000586

AC XY:

AN XY:

34139

show subpopulations

Gnomad AFR

AF:

0.0000650

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:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000628

AC:

AN:

175198

Hom.:

AF XY:

0.0000832

AC XY:

AN XY:

60082

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000115

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000118

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000762

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000998

AC:

108

AN:

1081993

Hom.:

AF XY:

0.000112

AC XY:

AN XY:

348079

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000116

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000581

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000112

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000357

AC:

AN:

111953

Hom.:

Cov.:

AF XY:

0.0000586

AC XY:

AN XY:

34139

show subpopulations

Gnomad4 AFR

AF:

0.0000650

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:

0.0000376

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000340

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 05, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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