rs5969896

Variant names:

• chrX-152430247-G-A
• rs5969896
• NM_000808.4:c.-27+20899C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-152430247-G-A
• chrX-152430247-G-C

Variant summary

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

The NM_000808.4(GABRA3):​c.-27+20899C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 111,114 control chromosomes in the GnomAD database, including 1,334 homozygotes. There are 5,793 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 0.18 (1334 hom., 5793 hem., cov: 23)
• Consequence: GABRA3 NM_000808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA3	NM_000808.4	c.-27+20899C>T		intron_variant	Intron 1 of 9	ENST00000370314.9	NP_000799.1
GABRA3	XM_006724811.4	c.-27+20899C>T		intron_variant	Intron 1 of 8		XP_006724874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA3	ENST00000370314.9	c.-27+20899C>T		intron_variant	Intron 1 of 9	1	NM_000808.4	ENSP00000359337.4

Frequencies

GnomAD3 genomes AF: 0.178 AC: 19741 AN: 111059 Hom.: 1336 Cov.: 23

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.0902

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.178 AC: 19759 AN: 111114 Hom.: 1334 Cov.: 23 AF XY: 0.173 AC XY: 5793 AN XY: 33412

African (AFR) AF: 0.188 AC: 5753 AN: 30555

American (AMR) AF: 0.173 AC: 1814 AN: 10478

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 431 AN: 2643

East Asian (EAS) AF: 0.375 AC: 1303 AN: 3476

South Asian (SAS) AF: 0.166 AC: 441 AN: 2663

European-Finnish (FIN) AF: 0.169 AC: 1000 AN: 5933

Middle Eastern (MID) AF: 0.226 AC: 48 AN: 212

European-Non Finnish (NFE) AF: 0.163 AC: 8626 AN: 52963

Other (OTH) AF: 0.186 AC: 282 AN: 1515

Alfa AF: 0.170 Hom.: 14161

Bravo AF: 0.185

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.36
DANN	Benign	0.30
PhyloP100		-0.17
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: rs5969896; hg19: chrX-151598719;