rs12833553

Positions:

• chrX-152242142-G-A
• chrX-152242142-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000808.4(GABRA3):​c.551+13636C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 110,910 control chromosomes in the GnomAD database, including 839 homozygotes. There are 4,684 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 0.14 (839 hom., 4684 hem., cov: 22)
• Consequence: GABRA3 NM_000808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA3	NM_000808.4	c.551+13636C>T		intron_variant		ENST00000370314.9	NP_000799.1
GABRA3	XM_006724811.4	c.551+13636C>T		intron_variant			XP_006724874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA3	ENST00000370314.9	c.551+13636C>T		intron_variant		1	NM_000808.4	ENSP00000359337	P1
GABRA3	ENST00000535043.1	c.551+13636C>T		intron_variant		1		ENSP00000443527	P1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 15535 AN: 110858 Hom.: 836 Cov.: 22 AF XY: 0.141 AC XY: 4671 AN XY: 33122

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.0778

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.140 AC: 15552 AN: 110910 Hom.: 839 Cov.: 22 AF XY: 0.141 AC XY: 4684 AN XY: 33184

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.0777

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.136

Alfa AF: 0.125 Hom.: 4530

Bravo AF: 0.147

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.8
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs12833553; hg19: chrX-151410614;