Variant chr9-113479508-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001394167.1(RGS3):c.97A>G(p.Ile33Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000322 in 1,614,188 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 1 hom. )

Consequence

RGS3
NM_001394167.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.54

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22971684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RGS3	NM_001394167.1 linkuse as main transcript	c.97A>G	p.Ile33Val	missense_variant	2/23	ENST00000695401.1
RGS3	NM_144488.8 linkuse as main transcript	c.121A>G	p.Ile41Val	missense_variant	5/26
RGS3	NM_017790.6 linkuse as main transcript	c.97A>G	p.Ile33Val	missense_variant	2/18
RGS3	NM_001282923.2 linkuse as main transcript	c.-4A>G		5_prime_UTR_variant	2/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS3	ENST00000695401.1 linkuse as main transcript	c.97A>G	p.Ile33Val	missense_variant	2/23		NM_001394167.1	P2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251478

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.0000426

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000359

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 03, 2022

The c.433A>G (p.I145V) alteration is located in exon 5 (coding exon 4) of the RGS3 gene. This alteration results from a A to G substitution at nucleotide position 433, causing the isoleucine (I) at amino acid position 145 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.059

T;T;.

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.90

M_CAP

Benign

0.050

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Uncertain

-0.26

MutationAssessor

Benign

0.93

L;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.17

N;N;N

REVEL

Benign

0.28

Sift

Benign

0.045

D;D;T

Sift4G

Benign

0.13

T;T;T

Polyphen

0.83

P;P;P

Vest4

0.35

MutPred

0.62

Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);.;

MVP

0.60

MPC

0.17

ClinPred

0.26

GERP RS

4.2

Varity_R

0.17

gMVP

0.075

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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