NM_002075.4:c.32C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002075.4(GNB3):c.32C>T(p.Ala11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,613,538 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 (★★). Synonymous variant affecting the same amino acid position (i.e. A11A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

GNB3
NM_002075.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 3.04

Publications

0 publications found

Variant links:

Genes affected

GNB3 (HGNC:4400): (G protein subunit beta 3) Heterotrimeric guanine nucleotide-binding proteins (G proteins), which integrate signals between receptors and effector proteins, are composed of an alpha, a beta, and a gamma subunit. These subunits are encoded by families of related genes. This gene encodes a beta subunit which belongs to the WD repeat G protein beta family. Beta subunits are important regulators of alpha subunits, as well as of certain signal transduction receptors and effectors. A single-nucleotide polymorphism (C825T) in this gene is associated with essential hypertension and obesity. This polymorphism is also associated with the occurrence of the splice variant GNB3-s, which appears to have increased activity. GNB3-s is an example of alternative splicing caused by a nucleotide change outside of the splice donor and acceptor sites. Alternative splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Jul 2014]

GNB3 Gene-Disease associations (from GenCC):

congenital stationary night blindness
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
congenital stationary night blindness 1H
Inheritance: AR, Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P

GNB3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09407815).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002075.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNB3	NM_002075.4	MANE Select	c.32C>T	p.Ala11Val	missense	Exon 2 of 10	NP_002066.1	P16520-1
	GNB3	NM_001297571.2		c.32C>T	p.Ala11Val	missense	Exon 2 of 10	NP_001284500.1	E9PCP0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GNB3	ENST00000229264.8	TSL:5 MANE Select	c.32C>T	p.Ala11Val	missense	Exon 2 of 10	ENSP00000229264.3	P16520-1
GNB3	ENST00000435982.6	TSL:1	c.32C>T	p.Ala11Val	missense	Exon 2 of 10	ENSP00000414734.2	E9PCP0
GNB3	ENST00000542868.1	TSL:1	n.279C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000642

AC:

AN:

249254

AF XY:

0.0000519

show subpopulations

Gnomad AFR exome

AF:

0.000499

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1461264

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

726862

show subpopulations

African (AFR)

AF:

0.000448

AC:

AN:

33474

American (AMR)

AF:

0.000112

AC:

AN:

44654

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.000101

AC:

AN:

39684

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86078

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1111718

Other (OTH)

AF:

0.0000331

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000177

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.000578

AC:

AN:

41538

American (AMR)

AF:

0.000131

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000274

Hom.:

Bravo

AF:

0.000272

ExAC

AF:

0.0000577

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.90

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.022

MetaRNN

Benign

0.094

MetaSVM

Benign

-0.86

MutationAssessor

Pathogenic

2.9

PhyloP100

3.0

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-2.2

REVEL

Benign

0.16

Sift

Uncertain

0.010

Sift4G

Benign

0.28

Polyphen

0.12

Vest4

0.25

MVP

0.55

MPC

0.24

ClinPred

0.13

GERP RS

4.8

PromoterAI

0.087

Neutral

(source)

Varity_R

0.27

gMVP

0.52

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over