Genetic Variant RGS3:n.3480T>C (chr9-113597059-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000487344.1(RGS3):n.3480T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 935,266 control chromosomes in the GnomAD database, including 283,653 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.78 ( 46949 hom., cov: 32)

Exomes 𝑓: 0.77 ( 236704 hom. )

Consequence

RGS3
ENST00000487344.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.149

Publications

12 publications found

Variant links:

Genes affected

RGS3 (HGNC:9999): (regulator of G protein signaling 3) This gene encodes a member of the regulator of G-protein signaling (RGS) family. This protein is a GTPase-activating protein that inhibits G-protein-mediated signal transduction. Alternative splicing and the use of alternative promoters results in multiple transcript variants encoding different isoforms. Long isoforms are largely cytosolic and plasma membrane-associated with a function in Wnt signaling and in the epithelial mesenchymal transition, while shorter N-terminally-truncated isoforms can be nuclear. [provided by RefSeq, Jan 2013]

RGS3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS3	NM_001394167.1 link	c.*106T>C		3_prime_UTR_variant	Exon 23 of 23	ENST00000695401.1	NP_001381096.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS3	ENST00000695401.1 link	c.*106T>C		3_prime_UTR_variant	Exon 23 of 23		NM_001394167.1	ENSP00000511882.1		A0A8Q3WKG2

Frequencies

GnomAD3 genomes

AF:

0.784

AC:

119207

AN:

151970

Hom.:

46928

Cov.:

show subpopulations

Gnomad AFR

AF:

0.795

Gnomad AMI

AF:

0.879

Gnomad AMR

AF:

0.838

Gnomad ASJ

AF:

0.787

Gnomad EAS

AF:

0.988

Gnomad SAS

AF:

0.843

Gnomad FIN

AF:

0.747

Gnomad MID

AF:

0.842

Gnomad NFE

AF:

0.750

Gnomad OTH

AF:

0.800

GnomAD4 exome

AF:

0.775

AC:

606623

AN:

783178

Hom.:

236704

Cov.:

AF XY:

0.778

AC XY:

311804

AN XY:

401024

show subpopulations

African (AFR)

AF:

0.795

AC:

15029

AN:

18902

American (AMR)

AF:

0.879

AC:

20314

AN:

23108

Ashkenazi Jewish (ASJ)

AF:

0.811

AC:

13059

AN:

16102

East Asian (EAS)

AF:

0.984

AC:

34353

AN:

34908

South Asian (SAS)

AF:

0.843

AC:

47929

AN:

56824

European-Finnish (FIN)

AF:

0.740

AC:

26931

AN:

36392

Middle Eastern (MID)

AF:

0.816

AC:

3345

AN:

4098

European-Non Finnish (NFE)

AF:

0.749

AC:

416418

AN:

555676

Other (OTH)

AF:

0.787

AC:

29245

AN:

37168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

6641

13282

19922

26563

33204

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.784

AC:

119272

AN:

152088

Hom.:

46949

Cov.:

AF XY:

0.788

AC XY:

58628

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.794

AC:

32938

AN:

41498

American (AMR)

AF:

0.838

AC:

12817

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.787

AC:

2732

AN:

3470

East Asian (EAS)

AF:

0.988

AC:

5088

AN:

5150

South Asian (SAS)

AF:

0.843

AC:

4067

AN:

4822

European-Finnish (FIN)

AF:

0.747

AC:

7917

AN:

10602

Middle Eastern (MID)

AF:

0.840

AC:

247

AN:

294

European-Non Finnish (NFE)

AF:

0.750

AC:

50970

AN:

67934

Other (OTH)

AF:

0.803

AC:

1696

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1331

2662

3992

5323

6654

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.776

Hom.:

31506

Bravo

AF:

0.794

Asia WGS

AF:

0.900

AC:

3130

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

0.15

Mutation Taster

=99/1

polymorphism (auto)

(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

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9-113597059-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over