rs12339493

Positions:

• chr9-113580764-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000374134.7(RGS3):​c.-413G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0983 in 981,102 control chromosomes in the GnomAD database, including 5,222 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 0.12 (1281 hom., cov: 33)
  • Exomes 𝑓: 0.095 (3941 hom.)
• Consequence: RGS3 ENST00000374134.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.641

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS3	NM_001394167.1	c.1702-2686G>A		intron_variant		ENST00000695401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS3	ENST00000695401.1	c.1702-2686G>A		intron_variant			NM_001394167.1	P2
	ENST00000428429.1	n.240+8337C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17981 AN: 152162 Hom.: 1265 Cov.: 33

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0620

Gnomad ASJ AF: 0.0729

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0418

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0974

Gnomad OTH AF: 0.0904

GnomAD4 exome AF: 0.0946 AC: 78421 AN: 828822 Hom.: 3941 Cov.: 17 AF XY: 0.0937 AC XY: 35884 AN XY: 382992

Gnomad4 AFR exome AF: 0.197

Gnomad4 AMR exome AF: 0.0440

Gnomad4 ASJ exome AF: 0.0559

Gnomad4 EAS exome AF: 0.000550

Gnomad4 SAS exome AF: 0.0435

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.0949

Gnomad4 OTH exome AF: 0.0819

GnomAD4 genome AF: 0.118 AC: 18043 AN: 152280 Hom.: 1281 Cov.: 33 AF XY: 0.118 AC XY: 8805 AN XY: 74466

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.0619

Gnomad4 ASJ AF: 0.0729

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0416

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.0974

Gnomad4 OTH AF: 0.0895

Alfa AF: 0.0933 Hom.: 704

Bravo AF: 0.112

Asia WGS AF: 0.0340 AC: 121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.3
DANN	Benign	0.86

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

LitVar

Other links and lift over

dbSNP: rs12339493; hg19: chr9-116343044;