Variant X-152652703-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_018558.4(GABRQ):c.1321C>A(p.Gln441Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,210,215 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 72 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., 15 hem., cov: 24)

Exomes 𝑓: 0.00011 ( 0 hom. 57 hem. )

Consequence

GABRQ
NM_018558.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.26

Variant links:

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]

GABRQ links:

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

MAGEA3-DT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047414303).

BP6

Variant X-152652703-C-A is Benign according to our data. Variant chrX-152652703-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3043692.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRQ	NM_018558.4 linkuse as main transcript	c.1321C>A	p.Gln441Lys	missense_variant	9/9	ENST00000598523.3
MAGEA3-DT	XR_938525.3 linkuse as main transcript	n.157-12909G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRQ	ENST00000598523.3 linkuse as main transcript	c.1321C>A	p.Gln441Lys	missense_variant	9/9	1	NM_018558.4	P1
MAGEA3-DT	ENST00000671457.1 linkuse as main transcript	n.130-12909G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

112627

Hom.:

Cov.:

AF XY:

0.000431

AC XY:

AN XY:

34783

show subpopulations

Gnomad AFR

AF:

0.000258

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000925

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00622

Gnomad SAS

AF:

0.000742

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000354

AC:

AN:

183362

Hom.:

AF XY:

0.000472

AC XY:

AN XY:

67808

show subpopulations

Gnomad AFR exome

AF:

0.000228

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00346

Gnomad SAS exome

AF:

0.000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000662

GnomAD4 exome

AF:

0.000111

AC:

122

AN:

1097536

Hom.:

Cov.:

AF XY:

0.000157

AC XY:

AN XY:

362892

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00199

Gnomad4 SAS exome

AF:

0.000517

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.000608

GnomAD4 genome

AF:

0.000302

AC:

AN:

112679

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

34845

show subpopulations

Gnomad4 AFR

AF:

0.000258

Gnomad4 AMR

AF:

0.0000924

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00624

Gnomad4 SAS

AF:

0.000745

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000689

Hom.:

Bravo

AF:

0.000170

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000461

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

GABRQ-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 31, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

Cadd

Benign

Dann

Benign

0.94

FATHMM_MKL

Benign

0.062

MetaRNN

Benign

0.0047

MetaSVM

Benign

-0.89

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

Sift4G

Benign

0.91

Vest4

0.062

MVP

0.74

ClinPred

0.010

GERP RS

1.4

gMVP

0.44

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over