chr9-113580764-G-A

Variant names:

• chr9-113580764-G-A
• rs12339493
• ENST00000374134.7:c.-413G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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]

ENSG00000237073 (HGNC:58614):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000374134.7. 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.1702-2686G>A		intron	N/A	NP_001381096.1
	RGS3	NM_144488.8		c.1726-2686G>A		intron	N/A	NP_652759.4
	RGS3	NM_001282923.2		c.1708-2686G>A		intron	N/A	NP_001269852.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS3	ENST00000374134.7	TSL:1	c.-413G>A		5_prime_UTR	Exon 1 of 8	ENSP00000363249.3
	RGS3	ENST00000695401.1	MANE Select	c.1702-2686G>A		intron	N/A	ENSP00000511882.1
	RGS3	ENST00000343817.9	TSL:1	c.1195-2686G>A		intron	N/A	ENSP00000340284.5

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

African (AFR) AF: 0.197 AC: 3096 AN: 15686

American (AMR) AF: 0.0440 AC: 43 AN: 978

Ashkenazi Jewish (ASJ) AF: 0.0559 AC: 286 AN: 5120

East Asian (EAS) AF: 0.000550 AC: 2 AN: 3636

South Asian (SAS) AF: 0.0435 AC: 713 AN: 16376

European-Finnish (FIN) AF: 0.160 AC: 49 AN: 306

Middle Eastern (MID) AF: 0.0665 AC: 107 AN: 1610

European-Non Finnish (NFE) AF: 0.0949 AC: 71899 AN: 757928

Other (OTH) AF: 0.0819 AC: 2226 AN: 27182

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

African (AFR) AF: 0.190 AC: 7878 AN: 41550

American (AMR) AF: 0.0619 AC: 947 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0729 AC: 253 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0416 AC: 201 AN: 4828

European-Finnish (FIN) AF: 0.181 AC: 1913 AN: 10598

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0974 AC: 6627 AN: 68024

Other (OTH) AF: 0.0895 AC: 189 AN: 2112

Alfa AF: 0.0954 Hom.: 1147

Bravo AF: 0.112

Asia WGS AF: 0.0340 AC: 121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.3
DANN	Benign	0.86
PhyloP100		-0.64
PromoterAI		0.025	Neutral
Mutation Taster		=100/0	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: rs12339493; hg19: chr9-116343044;