ENST00000350696.9:c.304C>T

Variant names:

• chr9-113462090-C-T
• rs373588536
• ENST00000350696.9:c.304C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000350696.9(RGS3):​c.304C>T​(p.Pro102Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000165 in 1,614,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: RGS3 ENST00000350696.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.500
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05294463).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000350696.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS3	NM_144488.8		c.-9C>T		5_prime_UTR	Exon 4 of 26	NP_652759.4	P49796-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS3	ENST00000350696.9	TSL:5	c.304C>T	p.Pro102Ser	missense	Exon 3 of 25	ENSP00000259406.7	P49796-3
	RGS3	ENST00000374140.6	TSL:2	c.304C>T	p.Pro102Ser	missense	Exon 4 of 26	ENSP00000363255.2	P49796-3

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152166 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000882 AC: 22 AN: 249516 AF XY: 0.0000960

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000168 AC: 245 AN: 1461844 Hom.: 0 Cov.: 32 AF XY: 0.000146 AC XY: 106 AN XY: 727218

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.000112 AC: 5 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.000210 AC: 234 AN: 1112010

Other (OTH) AF: 0.0000828 AC: 5 AN: 60388

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152284 Hom.: 0 Cov.: 31 AF XY: 0.000148 AC XY: 11 AN XY: 74446

African (AFR) AF: 0.0000241 AC: 1 AN: 41558

American (AMR) AF: 0.000196 AC: 3 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000197 Hom.: 0

Bravo AF: 0.000162

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000236 AC: 2

ExAC AF: 0.0000495 AC: 6

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.2
DANN	Benign	0.96
DEOGEN2	Benign	0.046	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.50
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.092
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.026	D
Polyphen		0.0010	B
Vest4		0.061
MVP		0.22
MPC		0.20
ClinPred		0.016	T
GERP RS		-0.27
Varity_R		0.084
gMVP		0.20
Mutation Taster		=100/0	polymorphism

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: rs373588536; hg19: chr9-116224370;