rs3810651

chrX-152652814-A-CchrX-152652814-A-GchrX-152652814-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018558.4(GABRQ):c.1432A>C(p.Ile478Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 6/8 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I478F) has been classified as Benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: GABRQ NM_018558.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.649

Genes affected

GABRQ (HGNC:14454): (gamma-aminobutyric acid type A receptor subunit theta) The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes the theta subunit of the GABA A receptor. The gene is mapped to chromosome Xq28 in a cluster of genes including those that encode the alpha 3 and epsilon subunits of the GABA A receptor. [provided by RefSeq, Jul 2017]

MAGEA3-DT (HGNC:56247): (MAGEA3 divergent transcript)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05260119).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRQ	NM_018558.4	c.1432A>C	p.Ile478Leu	missense_variant	9/9	ENST00000598523.3
MAGEA3-DT	XR_938525.3	n.157-13020T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRQ	ENST00000598523.3	c.1432A>C	p.Ile478Leu	missense_variant	9/9	1	NM_018558.4	P1
MAGEA3-DT	ENST00000671457.1	n.130-13020T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.035
MetaRNN	Benign	0.053	T
Sift4G	Benign	0.78	T
Vest4		0.075
gMVP		0.099

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3810651; hg19: chrX-151821277;