rs10218364

Variant names:

• chrX-152415658-G-A
• rs10218364
• NM_000808.4:c.-27+35488C>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.-27+35488C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 110,282 control chromosomes in the GnomAD database, including 2,262 homozygotes. There are 7,152 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 0.22 (2262 hom., 7152 hem., cov: 22)
• Consequence: GABRA3 NM_000808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.655
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA3	NM_000808.4	c.-27+35488C>T		intron_variant	Intron 1 of 9	ENST00000370314.9	NP_000799.1
GABRA3	XM_006724811.4	c.-27+35488C>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+35488C>T		intron_variant	Intron 1 of 9	1	NM_000808.4	ENSP00000359337.4

Frequencies

GnomAD3 genomes AF: 0.224 AC: 24724 AN: 110231 Hom.: 2254 Cov.: 22

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.279

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.224 AC: 24737 AN: 110282 Hom.: 2262 Cov.: 22 AF XY: 0.219 AC XY: 7152 AN XY: 32680

African (AFR) AF: 0.107 AC: 3279 AN: 30511

American (AMR) AF: 0.344 AC: 3541 AN: 10292

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 808 AN: 2627

East Asian (EAS) AF: 0.253 AC: 880 AN: 3481

South Asian (SAS) AF: 0.221 AC: 582 AN: 2629

European-Finnish (FIN) AF: 0.190 AC: 1112 AN: 5857

Middle Eastern (MID) AF: 0.266 AC: 57 AN: 214

European-Non Finnish (NFE) AF: 0.267 AC: 14027 AN: 52503

Other (OTH) AF: 0.245 AC: 365 AN: 1488

Alfa AF: 0.243 Hom.: 1995

Bravo AF: 0.232

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.57
DANN	Benign	0.78
PhyloP100		-0.66
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: rs10218364; hg19: chrX-151584130;