Variant 15-26977087-G-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_033223.5(GABRG3):c.139G>A(p.Val47Met) variant causes a missense change. The variant allele was found at a frequency of 0.00195 in 1,613,950 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 6 hom. )

Consequence

GABRG3
NM_033223.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.85

Variant links:

Genes affected

GABRG3 (HGNC:4088): (gamma-aminobutyric acid type A receptor subunit gamma3) This gene encodes a gamma-aminobutyric acid (GABA) receptor. 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. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. The protein encoded by this gene is a gamma subunit, which contains the benzodiazepine binding site. Two transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Aug 2012]

GABRG3 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=0.016829938).

BP6

Variant 15-26977087-G-A is Benign according to our data. Variant chr15-26977087-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 720823.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRG3	NM_033223.5 linkuse as main transcript	c.139G>A	p.Val47Met	missense_variant	2/10	ENST00000615808.5
GABRG3	NM_001270873.2 linkuse as main transcript	c.139G>A	p.Val47Met	missense_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRG3	ENST00000615808.5 linkuse as main transcript	c.139G>A	p.Val47Met	missense_variant	2/10	1	NM_033223.5	P1	Q99928-1
GABRG3	ENST00000555083.5 linkuse as main transcript	c.139G>A	p.Val47Met	missense_variant	2/6	2			Q99928-2
GABRG3	ENST00000553440.1 linkuse as main transcript	n.231G>A		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.00172

AC:

261

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00349

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00263

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00181

AC:

452

AN:

249254

Hom.:

AF XY:

0.00197

AC XY:

266

AN XY:

135224

show subpopulations

Gnomad AFR exome

AF:

0.000452

Gnomad AMR exome

AF:

0.00177

Gnomad ASJ exome

AF:

0.00358

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.00316

Gnomad NFE exome

AF:

0.00223

Gnomad OTH exome

AF:

0.00198

GnomAD4 exome

AF:

0.00198

AC:

2888

AN:

1461650

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

1425

AN XY:

727102

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.00159

Gnomad4 ASJ exome

AF:

0.00329

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000568

Gnomad4 FIN exome

AF:

0.00363

Gnomad4 NFE exome

AF:

0.00212

Gnomad4 OTH exome

AF:

0.00186

GnomAD4 genome

AF:

0.00171

AC:

261

AN:

152300

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

139

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00349

Gnomad4 NFE

AF:

0.00263

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00237

Hom.:

Bravo

AF:

0.00146

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000271

AC:

ESP6500EA

AF:

0.00245

AC:

ExAC

AF:

0.00179

AC:

216

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00229

EpiControl

AF:

0.00213

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

T;.

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.050

MetaRNN

Benign

0.017

T;T

MetaSVM

Uncertain

0.19

MutationAssessor

Benign

2.0

M;M

MutationTaster

Benign

0.98

D;D

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.1

.;N

REVEL

Uncertain

0.33

Sift

Benign

0.033

.;D

Sift4G

Uncertain

0.016

D;D

Polyphen

0.99

D;.

Vest4

0.45

MVP

0.56

ClinPred

0.016

GERP RS

5.3

Varity_R

0.12

gMVP

0.53

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