Variant rs739999 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_183337.3(RGS11):c.1280T>C(p.Met427Thr) variant causes a missense change. The variant allele was found at a frequency of 0.125 in 1,612,686 control chromosomes in the GnomAD database, including 23,660 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.24 ( 7803 hom., cov: 34)

Exomes 𝑓: 0.11 ( 15857 hom. )

Consequence

RGS11
NM_183337.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.41

Variant links:

Genes affected

RGS11 (HGNC:9993): (regulator of G protein signaling 11) The protein encoded by this gene belongs to the RGS (regulator of G protein signaling) family. Members of the RGS family act as GTPase-activating proteins on the alpha subunits of heterotrimeric, signal-transducing G proteins. This protein inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. Alternative splicing occurs at this locus and four transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Nov 2013]

RGS11 links:

FAM234A (HGNC:14163): (family with sequence similarity 234 member A) Located in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

FAM234A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.5902107E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS11	NM_183337.3 linkuse as main transcript	c.1280T>C	p.Met427Thr	missense_variant	16/17	ENST00000397770.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS11	ENST00000397770.8 linkuse as main transcript	c.1280T>C	p.Met427Thr	missense_variant	16/17	1	NM_183337.3	P2	O94810-1

Frequencies

GnomAD3 genomes

AF:

0.241

AC:

36703

AN:

152116

Hom.:

7762

Cov.:

show subpopulations

Gnomad AFR

AF:

0.563

Gnomad AMI

AF:

0.135

Gnomad AMR

AF:

0.219

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.324

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.0550

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.0864

Gnomad OTH

AF:

0.214

GnomAD3 exomes

AF:

0.173

AC:

43253

AN:

250050

Hom.:

6464

AF XY:

0.156

AC XY:

21214

AN XY:

135574

show subpopulations

Gnomad AFR exome

AF:

0.580

Gnomad AMR exome

AF:

0.303

Gnomad ASJ exome

AF:

0.212

Gnomad EAS exome

AF:

0.324

Gnomad SAS exome

AF:

0.119

Gnomad FIN exome

AF:

0.0530

Gnomad NFE exome

AF:

0.0858

Gnomad OTH exome

AF:

0.148

GnomAD4 exome

AF:

0.113

AC:

164345

AN:

1460452

Hom.:

15857

Cov.:

AF XY:

0.111

AC XY:

80395

AN XY:

726572

show subpopulations

Gnomad4 AFR exome

AF:

0.579

Gnomad4 AMR exome

AF:

0.292

Gnomad4 ASJ exome

AF:

0.207

Gnomad4 EAS exome

AF:

0.299

Gnomad4 SAS exome

AF:

0.122

Gnomad4 FIN exome

AF:

0.0526

Gnomad4 NFE exome

AF:

0.0822

Gnomad4 OTH exome

AF:

0.148

GnomAD4 genome

AF:

0.242

AC:

36793

AN:

152234

Hom.:

7803

Cov.:

AF XY:

0.237

AC XY:

17677

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.564

Gnomad4 AMR

AF:

0.219

Gnomad4 ASJ

AF:

0.195

Gnomad4 EAS

AF:

0.323

Gnomad4 SAS

AF:

0.123

Gnomad4 FIN

AF:

0.0550

Gnomad4 NFE

AF:

0.0864

Gnomad4 OTH

AF:

0.213

Alfa

AF:

0.129

Hom.:

4592

Bravo

AF:

0.275

TwinsUK

AF:

0.0717

AC:

266

ALSPAC

AF:

0.0848

AC:

327

ESP6500AA

AF:

0.550

AC:

2422

ESP6500EA

AF:

0.0894

AC:

769

ExAC

AF:

0.174

AC:

21133

Asia WGS

AF:

0.220

AC:

762

AN:

3478

EpiCase

AF:

0.0954

EpiControl

AF:

0.0981

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

Cadd

Benign

7.1

Dann

Benign

0.55

DEOGEN2

Benign

0.074

T;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.18

T;T;T

MetaRNN

Benign

0.000016

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-2.2

N;.;.

MutationTaster

Benign

1.3e-10

P;P;P;P

PrimateAI

Benign

0.36

PROVEAN

Benign

2.6

N;N;N

REVEL

Benign

0.077

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.037

MPC

0.11

ClinPred

0.0024

GERP RS

3.5

Varity_R

0.023

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over