chrX-152242142-G-A

Variant names:

• chrX-152242142-G-A
• rs12833553
• NM_000808.4:c.551+13636C>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.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
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.216 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA3	NM_000808.4	MANE Select	c.551+13636C>T		intron	N/A	NP_000799.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA3	ENST00000370314.9	TSL:1 MANE Select	c.551+13636C>T		intron	N/A	ENSP00000359337.4
	GABRA3	ENST00000535043.1	TSL:1	c.551+13636C>T		intron	N/A	ENSP00000443527.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 15535 AN: 110858 Hom.: 836 Cov.: 22

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

African (AFR) AF: 0.115 AC: 3507 AN: 30524

American (AMR) AF: 0.223 AC: 2326 AN: 10409

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 414 AN: 2642

East Asian (EAS) AF: 0.0777 AC: 272 AN: 3499

South Asian (SAS) AF: 0.198 AC: 520 AN: 2620

European-Finnish (FIN) AF: 0.157 AC: 925 AN: 5907

Middle Eastern (MID) AF: 0.121 AC: 26 AN: 215

European-Non Finnish (NFE) AF: 0.135 AC: 7118 AN: 52909

Other (OTH) AF: 0.136 AC: 207 AN: 1517

Alfa AF: 0.132 Hom.: 6302

Bravo AF: 0.147

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.8
DANN	Benign	0.34
PhyloP100		1.4
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: rs12833553; hg19: chrX-151410614;