Variant 6-89178937-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002042.5(GABRR1):c.1273G>A(p.Val425Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,614,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

GABRR1
NM_002042.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.99

Variant links:

Genes affected

GABRR1 (HGNC:4090): (gamma-aminobutyric acid type A receptor subunit rho1) GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA receptors, which are ligand-gated chloride channels. GABRR1 is a member of the rho subunit family. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

GABRR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12229571).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRR1	NM_002042.5 linkuse as main transcript	c.1273G>A	p.Val425Met	missense_variant	10/10	ENST00000454853.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRR1	ENST00000454853.7 linkuse as main transcript	c.1273G>A	p.Val425Met	missense_variant	10/10	1	NM_002042.5	P1	P24046-1
GABRR1	ENST00000435811.5 linkuse as main transcript	c.1222G>A	p.Val408Met	missense_variant	9/9	2			P24046-2
GABRR1	ENST00000369451.7 linkuse as main transcript	c.1012G>A	p.Val338Met	missense_variant	12/12	5			P24046-3
GABRR1	ENST00000457434.1 linkuse as main transcript	c.*1234G>A		3_prime_UTR_variant, NMD_transcript_variant	11/11	5

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.0000835

AC:

AN:

251404

Hom.:

AF XY:

0.0000883

AC XY:

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000956

Bravo

AF:

0.0000793

ExAC

AF:

0.0000494

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2023

The c.1273G>A (p.V425M) alteration is located in exon 10 (coding exon 10) of the GABRR1 gene. This alteration results from a G to A substitution at nucleotide position 1273, causing the valine (V) at amino acid position 425 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.17

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.082

T;.;.;.;.

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

D;D;.;D;.

M_CAP

Benign

0.051

MetaRNN

Benign

0.12

T;T;T;T;T

MetaSVM

Uncertain

0.30

MutationAssessor

Benign

1.2

L;.;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.73

N;N;.;.;N

REVEL

Uncertain

0.39

Sift

Benign

0.049

D;T;.;.;T

Sift4G

Benign

0.24

T;T;T;T;T

Polyphen

0.98

D;D;.;.;.

Vest4

0.12

MutPred

0.46

Loss of sheet (P = 0.0315);.;.;.;.;

MVP

0.95

MPC

0.39

ClinPred

0.15

GERP RS

5.7

Varity_R

0.15

gMVP

0.58

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

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