chr16-269291-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_183337.3(RGS11):c.1382G>A(p.Gly461Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000633 in 1,579,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

RGS11
NM_183337.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.869

Publications

2 publications found

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:

ENSG00000286901 (HGNC:):

ENSG00000286901 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.031414986).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183337.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RGS11	NM_183337.3	MANE Select	c.1382G>A	p.Gly461Glu	missense	Exon 17 of 17	NP_899180.1	O94810-1
RGS11	NM_001286485.2		c.1349G>A	p.Gly450Glu	missense	Exon 16 of 16	NP_001273414.1	O94810-2
RGS11	NM_003834.3		c.1319G>A	p.Gly440Glu	missense	Exon 17 of 17	NP_003825.1	O94810-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RGS11	ENST00000397770.8	TSL:1 MANE Select	c.1382G>A	p.Gly461Glu	missense	Exon 17 of 17	ENSP00000380876.3	O94810-1
RGS11	ENST00000359740.6	TSL:1	c.1349G>A	p.Gly450Glu	missense	Exon 16 of 16	ENSP00000352778.5	O94810-2
RGS11	ENST00000316163.9	TSL:1	c.1319G>A	p.Gly440Glu	missense	Exon 17 of 17	ENSP00000319069.5	O94810-3

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000513

AC:

AN:

194804

AF XY:

0.00000952

show subpopulations

Gnomad AFR exome

AF:

0.0000875

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000280

AC:

AN:

1427372

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

706790

show subpopulations

African (AFR)

AF:

0.0000302

AC:

AN:

33090

American (AMR)

AF:

0.00

AC:

AN:

38786

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25402

East Asian (EAS)

AF:

0.00

AC:

AN:

38400

South Asian (SAS)

AF:

0.00

AC:

AN:

81652

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49778

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4884

European-Non Finnish (NFE)

AF:

9.12e-7

AC:

AN:

1096280

Other (OTH)

AF:

0.0000338

AC:

AN:

59100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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:

0.0000394

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41478

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

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:

0.0000434

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000168

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.55

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.080

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.36

M_CAP

Benign

0.0022

MetaRNN

Benign

0.031

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

-0.87

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.070

REVEL

Benign

0.017

Sift

Benign

0.74

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.083

MutPred

0.25

Gain of solvent accessibility (P = 0.012)

MVP

0.14

MPC

0.13

ClinPred

0.55

GERP RS

-7.5

Varity_R

0.036

gMVP

0.25

Mutation Taster

=100/0

polymorphism

(source)

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

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