rs5970223

Variant names:

• chrX-152191507-T-G
• rs5970223
• NM_000808.4:c.932-1566A>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.932-1566A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.33 (5023 hom., 9542 hem., cov: 20)
• Consequence: GABRA3 NM_000808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315
• Publications: 2 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: Illumina, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000808.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA3	NM_000808.4	MANE Select	c.932-1566A>C		intron	N/A	NP_000799.1	P34903

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA3	ENST00000370314.9	TSL:1 MANE Select	c.932-1566A>C		intron	N/A	ENSP00000359337.4	P34903
	GABRA3	ENST00000535043.1	TSL:1	c.932-1566A>C		intron	N/A	ENSP00000443527.1	P34903
	GABRA3	ENST00000862742.1		c.932-1566A>C		intron	N/A	ENSP00000532801.1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 35792 AN: 108149 Hom.: 5023 Cov.: 20

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.331 AC: 35825 AN: 108203 Hom.: 5023 Cov.: 20 AF XY: 0.311 AC XY: 9542 AN XY: 30655

African (AFR) AF: 0.526 AC: 15515 AN: 29497

American (AMR) AF: 0.322 AC: 3191 AN: 9903

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 370 AN: 2620

East Asian (EAS) AF: 0.163 AC: 555 AN: 3414

South Asian (SAS) AF: 0.342 AC: 836 AN: 2448

European-Finnish (FIN) AF: 0.218 AC: 1205 AN: 5521

Middle Eastern (MID) AF: 0.308 AC: 65 AN: 211

European-Non Finnish (NFE) AF: 0.254 AC: 13312 AN: 52459

Other (OTH) AF: 0.320 AC: 468 AN: 1461

Alfa AF: 0.290 Hom.: 16291

Bravo AF: 0.351

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.68
PhyloP100		-0.32
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs5970223;

hg19: chrX-151359979;