Variant 16-269548-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_183337.3(RGS11):c.1244A>G(p.Lys415Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00536 in 1,613,380 control chromosomes in the GnomAD database, including 366 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 52 hom., cov: 33)

Exomes 𝑓: 0.0048 ( 314 hom. )

Consequence

RGS11
NM_183337.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0510

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 16-269548-T-C is Benign according to our data. Variant chr16-269548-T-C is described in ClinVar as [Benign]. Clinvar id is 1245849.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.113 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.1244A>G	p.Lys415Arg	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.1244A>G	p.Lys415Arg	missense_variant	16/17	1	NM_183337.3	P2	O94810-1

Frequencies

GnomAD3 genomes

AF:

0.0110

AC:

1678

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00864

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.00683

Gnomad FIN

AF:

0.00254

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.0140

AC:

3500

AN:

250708

Hom.:

165

AF XY:

0.0120

AC XY:

1630

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.0209

Gnomad AMR exome

AF:

0.0177

Gnomad ASJ exome

AF:

0.00358

Gnomad EAS exome

AF:

0.122

Gnomad SAS exome

AF:

0.00395

Gnomad FIN exome

AF:

0.00291

Gnomad NFE exome

AF:

0.000468

Gnomad OTH exome

AF:

0.00719

GnomAD4 exome

AF:

0.00476

AC:

6959

AN:

1461078

Hom.:

314

Cov.:

AF XY:

0.00457

AC XY:

3323

AN XY:

726868

show subpopulations

Gnomad4 AFR exome

AF:

0.0181

Gnomad4 AMR exome

AF:

0.0155

Gnomad4 ASJ exome

AF:

0.00322

Gnomad4 EAS exome

AF:

0.108

Gnomad4 SAS exome

AF:

0.00495

Gnomad4 FIN exome

AF:

0.00313

Gnomad4 NFE exome

AF:

0.000235

Gnomad4 OTH exome

AF:

0.00697

GnomAD4 genome

AF:

0.0110

AC:

1682

AN:

152302

Hom.:

Cov.:

AF XY:

0.0115

AC XY:

854

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0193

Gnomad4 AMR

AF:

0.00863

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.121

Gnomad4 SAS

AF:

0.00683

Gnomad4 FIN

AF:

0.00254

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.00994

Alfa

AF:

0.00527

Hom.:

Bravo

AF:

0.0129

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0197

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.0130

AC:

1574

Asia WGS

AF:

0.0420

AC:

144

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 25, 2021

This variant is associated with the following publications: (PMID: 28787443) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.75

Cadd

Benign

Dann

Benign

0.87

DEOGEN2

Benign

0.15

T;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.71

T;T;T

MetaRNN

Benign

0.0022

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.4

L;.;.

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.055

Sift

Benign

0.26

T;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.053

B;.;B

Vest4

0.042

MPC

0.082

ClinPred

0.0033

GERP RS

-4.9

Varity_R

0.097

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.28

Position offset: -1

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