X-152443154-A-T

Variant names:

• chrX-152443154-A-T
• rs10482215
• NM_000808.4:c.-27+7992T>A

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+7992T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 111,234 control chromosomes in the GnomAD database, including 1,478 homozygotes. There are 6,068 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 0.19 (1478 hom., 6068 hem., cov: 23)
• Consequence: GABRA3 NM_000808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.548
• 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: 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.36 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.-27+7992T>A		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.-27+7992T>A		intron	N/A	ENSP00000359337.4	P34903
	GABRA3	ENST00000862742.1		c.-101+7992T>A		intron	N/A	ENSP00000532801.1
	GABRA3	ENST00000862743.1		c.-98+7992T>A		intron	N/A	ENSP00000532802.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 20857 AN: 111188 Hom.: 1480 Cov.: 23

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.0938

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.254

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.188 AC: 20871 AN: 111234 Hom.: 1478 Cov.: 23 AF XY: 0.181 AC XY: 6068 AN XY: 33496

African (AFR) AF: 0.190 AC: 5847 AN: 30704

American (AMR) AF: 0.185 AC: 1952 AN: 10526

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 448 AN: 2639

East Asian (EAS) AF: 0.377 AC: 1327 AN: 3522

South Asian (SAS) AF: 0.172 AC: 465 AN: 2707

European-Finnish (FIN) AF: 0.173 AC: 1019 AN: 5895

Middle Eastern (MID) AF: 0.241 AC: 51 AN: 212

European-Non Finnish (NFE) AF: 0.178 AC: 9409 AN: 52844

Other (OTH) AF: 0.192 AC: 289 AN: 1503

Alfa AF: 0.177 Hom.: 1011

Bravo AF: 0.195

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.14
DANN	Benign	0.21
PhyloP100		-0.55
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: rs10482215; hg19: chrX-151611626;