9-113594236-A-G

Variant names:

• chr9-113594236-A-G
• rs12341266
• ENST00000620489.1:c.-41A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000620489.1(RGS3):​c.-41A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.898 in 1,612,388 control chromosomes in the GnomAD database, including 651,721 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 0.92 (65070 hom., cov: 32)
  • Exomes 𝑓: 0.90 (586651 hom.)
• Consequence: RGS3 ENST00000620489.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234
• Publications: 31 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=1.0136099E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000620489.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS3	NM_001394167.1	MANE Select	c.2745-194A>G		intron	N/A	NP_001381096.1
	RGS3	NM_144489.4		c.-41A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_652760.3
	RGS3	NM_001276262.2		c.-61A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_001263191.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS3	ENST00000620489.1	TSL:1	c.-41A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000479017.1
	RGS3	ENST00000620489.1	TSL:1	c.-41A>G		5_prime_UTR	Exon 1 of 5	ENSP00000479017.1
	RGS3	ENST00000695401.1	MANE Select	c.2745-194A>G		intron	N/A	ENSP00000511882.1

Frequencies

GnomAD3 genomes AF: 0.923 AC: 140453 AN: 152088 Hom.: 65008 Cov.: 32

Gnomad AFR AF: 0.977

Gnomad AMI AF: 0.953

Gnomad AMR AF: 0.912

Gnomad ASJ AF: 0.932

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.972

Gnomad FIN AF: 0.937

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.882

Gnomad OTH AF: 0.917

GnomAD2 exomes AF: 0.926 AC: 230715 AN: 249258 AF XY: 0.924

Gnomad AFR exome AF: 0.979

Gnomad AMR exome AF: 0.942

Gnomad ASJ exome AF: 0.939

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.938

Gnomad NFE exome AF: 0.885

Gnomad OTH exome AF: 0.908

GnomAD4 exome AF: 0.896 AC: 1307698 AN: 1460182 Hom.: 586651 Cov.: 70 AF XY: 0.898 AC XY: 651916 AN XY: 726314

African (AFR) AF: 0.981 AC: 32832 AN: 33480

American (AMR) AF: 0.941 AC: 42048 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 24482 AN: 26104

East Asian (EAS) AF: 1.00 AC: 39689 AN: 39694

South Asian (SAS) AF: 0.972 AC: 83828 AN: 86234

European-Finnish (FIN) AF: 0.937 AC: 48913 AN: 52188

Middle Eastern (MID) AF: 0.915 AC: 5279 AN: 5768

European-Non Finnish (NFE) AF: 0.878 AC: 975705 AN: 1111672

Other (OTH) AF: 0.910 AC: 54922 AN: 60356

GnomAD4 genome AF: 0.924 AC: 140574 AN: 152206 Hom.: 65070 Cov.: 32 AF XY: 0.927 AC XY: 68937 AN XY: 74390

African (AFR) AF: 0.977 AC: 40594 AN: 41556

American (AMR) AF: 0.913 AC: 13959 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.932 AC: 3237 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5151 AN: 5154

South Asian (SAS) AF: 0.973 AC: 4690 AN: 4822

European-Finnish (FIN) AF: 0.937 AC: 9934 AN: 10604

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.882 AC: 59931 AN: 67984

Other (OTH) AF: 0.918 AC: 1939 AN: 2112

Alfa AF: 0.899 Hom.: 46806

Bravo AF: 0.923

TwinsUK AF: 0.867 AC: 3214

ALSPAC AF: 0.865 AC: 3333

ESP6500AA AF: 0.976 AC: 4298

ESP6500EA AF: 0.882 AC: 7585

ExAC AF: 0.925 AC: 112298

Asia WGS AF: 0.986 AC: 3430 AN: 3478

EpiCase AF: 0.885

EpiControl AF: 0.879

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.5
DANN	Benign	0.42
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.0000010	T
MetaSVM	Benign	-0.93	T
PhyloP100		0.23
PROVEAN	Benign	0.16	N
REVEL	Benign	0.11
Sift	Benign	1.0	T
Sift4G	Benign	0.22	T
Vest4		0.010
ClinPred		0.0017	T
GERP RS		-1.2
PromoterAI		-0.0094	Neutral
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12341266; hg19: chr9-116356516; COSMIC: COSV59517625; COSMIC: COSV59517625;