Genetic Variant RGS11:p.Gly362Arg (chr16-270645-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_183337.3(RGS11):c.1084G>A(p.Gly362Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000317 in 1,609,542 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 (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

RGS11
NM_183337.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.63

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:

ENSG00000286901 (HGNC:):

ENSG00000286901 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 was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3063329).

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.1084G>A	p.Gly362Arg	missense	Exon 15 of 17	NP_899180.1	O94810-1
RGS11	NM_001286485.2		c.1051G>A	p.Gly351Arg	missense	Exon 14 of 16	NP_001273414.1	O94810-2
RGS11	NM_003834.3		c.1021G>A	p.Gly341Arg	missense	Exon 15 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.1084G>A	p.Gly362Arg	missense	Exon 15 of 17	ENSP00000380876.3	O94810-1
RGS11	ENST00000359740.6	TSL:1	c.1051G>A	p.Gly351Arg	missense	Exon 14 of 16	ENSP00000352778.5	O94810-2
RGS11	ENST00000316163.9	TSL:1	c.1021G>A	p.Gly341Arg	missense	Exon 15 of 17	ENSP00000319069.5	O94810-3

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00116

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:

0.0000877

AC:

AN:

239542

AF XY:

0.000123

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000895

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000186

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000295

AC:

AN:

1457270

Hom.:

Cov.:

AF XY:

0.0000262

AC XY:

AN XY:

724634

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33416

American (AMR)

AF:

0.00

AC:

AN:

44242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26018

East Asian (EAS)

AF:

0.000506

AC:

AN:

39528

South Asian (SAS)

AF:

0.000105

AC:

AN:

85536

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51908

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

1110668

Other (OTH)

AF:

0.0000332

AC:

AN:

60194

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.0000525

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41548

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.544

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:

0.00

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.0000827

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

Uncertain

0.37

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.47

MutationAssessor

Uncertain

2.7

PhyloP100

3.6

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-6.9

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.57

MutPred

0.52

Loss of sheet (P = 0.0817)

MVP

0.64

MPC

0.24

ClinPred

0.45

GERP RS

4.3

Varity_R

0.85

gMVP

0.33

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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