rs5925155

Variant names:

• chrX-152289446-G-A
• rs5925155
• NM_000808.4:c.263-4711C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-152289446-G-A
• chrX-152289446-G-C
• chrX-152289446-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000808.4(GABRA3):​c.263-4711C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 107,861 control chromosomes in the GnomAD database, including 10,096 homozygotes. There are 13,404 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (10096 hom., 13404 hem., cov: 21)
• Consequence: GABRA3 NM_000808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

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

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA3	NM_000808.4	c.263-4711C>T		intron_variant	Intron 3 of 9	ENST00000370314.9	NP_000799.1
GABRA3	XM_006724811.4	c.263-4711C>T		intron_variant	Intron 3 of 8		XP_006724874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA3	ENST00000370314.9	c.263-4711C>T		intron_variant	Intron 3 of 9	1	NM_000808.4	ENSP00000359337.4
GABRA3	ENST00000535043.1	c.263-4711C>T		intron_variant	Intron 3 of 9	1		ENSP00000443527.1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 48203 AN: 107841 Hom.: 10101 Cov.: 21

Gnomad AFR AF: 0.0985

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.441

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.447 AC: 48182 AN: 107861 Hom.: 10096 Cov.: 21 AF XY: 0.438 AC XY: 13404 AN XY: 30629

African (AFR) AF: 0.0983 AC: 2931 AN: 29823

American (AMR) AF: 0.513 AC: 5131 AN: 10010

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 1631 AN: 2607

East Asian (EAS) AF: 0.118 AC: 400 AN: 3378

South Asian (SAS) AF: 0.260 AC: 649 AN: 2492

European-Finnish (FIN) AF: 0.604 AC: 3051 AN: 5055

Middle Eastern (MID) AF: 0.488 AC: 102 AN: 209

European-Non Finnish (NFE) AF: 0.639 AC: 33342 AN: 52145

Other (OTH) AF: 0.437 AC: 645 AN: 1476

Alfa AF: 0.453 Hom.: 19196

Bravo AF: 0.423

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.30
DANN	Benign	0.44
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5925155; hg19: chrX-151457918;