X-152647124-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_018558.4(GABRQ):c.483C>T(p.Arg161=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,208,747 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000013 (0 hom. 3 hem.)
• Consequence: GABRQ NM_018558.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.66

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 Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant X-152647124-C-T is Benign according to our data. Variant chrX-152647124-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2661667.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.66 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRQ	NM_018558.4	c.483C>T	p.Arg161=	synonymous_variant	4/9	ENST00000598523.3
MAGEA3-DT	XR_938525.3	n.157-7330G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRQ	ENST00000598523.3	c.483C>T	p.Arg161=	synonymous_variant	4/9	1	NM_018558.4	P1
MAGEA3-DT	ENST00000671457.1	n.130-7330G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00000893 AC: 1 AN: 111970 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34124

Gnomad AFR AF: 0.00

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000128 AC: 14 AN: 1096777 Hom.: 0 Cov.: 30 AF XY: 0.00000828 AC XY: 3 AN XY: 362157

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000119

Gnomad4 OTH exome AF: 0.0000652

GnomAD4 genome AF: 0.00000893 AC: 1 AN: 111970 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34124

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000188

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

GABRQ: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	0.36
Dann	Benign	0.87

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: rs1930909080; hg19: chrX-151815585;