X-152242142-G-T

Variant names:

• chrX-152242142-G-T
• rs12833553
• NM_000808.4:c.551+13636C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000808.4(GABRA3):​c.551+13636C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 110,907 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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 0.000018 (0 hom., 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

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>A		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>A		intron	N/A	ENSP00000359337.4
	GABRA3	ENST00000535043.1	TSL:1	c.551+13636C>A		intron	N/A	ENSP00000443527.1

Frequencies

GnomAD3 genomes AF: 0.0000180 AC: 2 AN: 110907 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000656

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000180 AC: 2 AN: 110907 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33143

African (AFR) AF: 0.0000656 AC: 2 AN: 30478

American (AMR) AF: 0.00 AC: 0 AN: 10402

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2642

East Asian (EAS) AF: 0.00 AC: 0 AN: 3510

South Asian (SAS) AF: 0.00 AC: 0 AN: 2628

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5911

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52932

Other (OTH) AF: 0.00 AC: 0 AN: 1497

Alfa AF: 0.00 Hom.: 6302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.3
DANN	Benign	0.35
PhyloP100		1.4

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;