rs34797451

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003835.4(RGS9):c.1502G>A(p.Arg501His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.017 in 1,613,616 control chromosomes in the GnomAD database, including 292 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R501L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.011 ( 15 hom., cov: 32)

Exomes 𝑓: 0.018 ( 277 hom. )

Consequence

RGS9
NM_003835.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.604

Publications

10 publications found

Variant links:

Genes affected

RGS9 (HGNC:10004): (regulator of G protein signaling 9) This gene encodes a member of the RGS family of GTPase activating proteins that function in various signaling pathways by accelerating the deactivation of G proteins. This protein is anchored to photoreceptor membranes in retinal cells and deactivates G proteins in the rod and cone phototransduction cascades. Mutations in this gene result in bradyopsia. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

RGS9 Gene-Disease associations (from GenCC):

prolonged electroretinal response suppression 1
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
bradyopsia
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia

RGS9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004187554).

BP6

Variant 17-65225096-G-A is Benign according to our data. Variant chr17-65225096-G-A is described in ClinVar as Benign. ClinVar VariationId is 94379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0114 (1735/152086) while in subpopulation NFE AF = 0.0195 (1327/67948). AF 95% confidence interval is 0.0187. There are 15 homozygotes in GnomAd4. There are 791 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS9	NM_003835.4 link	c.1502G>A	p.Arg501His	missense_variant	Exon 18 of 19	ENST00000262406.10	NP_003826.2
RGS9	NM_001081955.3 link	c.1493G>A	p.Arg498His	missense_variant	Exon 18 of 19		NP_001075424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS9	ENST00000262406.10 link	c.1502G>A	p.Arg501His	missense_variant	Exon 18 of 19	1	NM_003835.4	ENSP00000262406.9

Frequencies

GnomAD3 genomes

AF:

0.0114

AC:

1735

AN:

151970

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00368

Gnomad AMI

AF:

0.00549

Gnomad AMR

AF:

0.00858

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00782

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0195

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.0107

AC:

2668

AN:

249178

AF XY:

0.0104

show subpopulations

Gnomad AFR exome

AF:

0.00329

Gnomad AMR exome

AF:

0.00559

Gnomad ASJ exome

AF:

0.000795

Gnomad EAS exome

AF:

0.000723

Gnomad FIN exome

AF:

0.00879

Gnomad NFE exome

AF:

0.0185

Gnomad OTH exome

AF:

0.00941

GnomAD4 exome

AF:

0.0175

AC:

25623

AN:

1461530

Hom.:

277

Cov.:

AF XY:

0.0169

AC XY:

12288

AN XY:

727092

show subpopulations

African (AFR)

AF:

0.00254

AC:

AN:

33480

American (AMR)

AF:

0.00539

AC:

241

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000727

AC:

AN:

26132

East Asian (EAS)

AF:

0.000302

AC:

AN:

39700

South Asian (SAS)

AF:

0.00184

AC:

159

AN:

86258

European-Finnish (FIN)

AF:

0.00879

AC:

467

AN:

53108

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0214

AC:

23805

AN:

1111966

Other (OTH)

AF:

0.0138

AC:

834

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

1613

3226

4838

6451

8064

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

896

1792

2688

3584

4480

<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:

0.0114

AC:

1735

AN:

152086

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

791

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.00366

AC:

152

AN:

41480

American (AMR)

AF:

0.00857

AC:

131

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3464

East Asian (EAS)

AF:

0.00116

AC:

AN:

5178

South Asian (SAS)

AF:

0.00104

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00782

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0195

AC:

1327

AN:

67948

Other (OTH)

AF:

0.0104

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

162

244

325

406

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.0159

Hom.:

Bravo

AF:

0.0106

TwinsUK

AF:

0.0194

AC:

ESP6500AA

AF:

0.00466

AC:

ESP6500EA

AF:

0.0181

AC:

152

ExAC

AF:

0.0108

AC:

1311

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0149

EpiControl

AF:

0.0170

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

not specified

Benign:1

Aug 01, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0067

T;.;.;T

Eigen

Benign

0.027

Eigen_PC

Benign

0.12

LIST_S2

Benign

0.85

T;T;T;T

MetaRNN

Benign

0.0042

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;.;.;L

PhyloP100

0.60

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.0

.;.;N;N

Sift

Pathogenic

0.0

.;.;D;D

Sift4G

Pathogenic

0.0

.;D;D;D

Vest4

0.0

ClinPred

0.019

GERP RS

3.9

Varity_R

0.15

gMVP

0.43

Mutation Taster

=99/1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over