chr9-113597059-T-C

Variant names:

• chr9-113597059-T-C
• rs1051013
• ENST00000487344.1:n.3480T>C

Variant summary

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

The ENST00000695401.1(RGS3):​c.*106T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 935,266 control chromosomes in the GnomAD database, including 283,653 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 0.78 (46949 hom., cov: 32)
  • Exomes 𝑓: 0.77 (236704 hom.)
• Consequence: RGS3 ENST00000695401.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149
• Publications: 12 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 (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000695401.1. 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.*106T>C		3_prime_UTR	Exon 23 of 23	NP_001381096.1
	RGS3	NM_144488.8		c.*106T>C		3_prime_UTR	Exon 26 of 26	NP_652759.4
	RGS3	NM_001282923.2		c.*106T>C		3_prime_UTR	Exon 23 of 23	NP_001269852.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS3	ENST00000487344.1	TSL:1	n.3480T>C		non_coding_transcript_exon	Exon 6 of 6
	RGS3	ENST00000695401.1	MANE Select	c.*106T>C		3_prime_UTR	Exon 23 of 23	ENSP00000511882.1
	RGS3	ENST00000343817.9	TSL:1	c.*106T>C		3_prime_UTR	Exon 16 of 16	ENSP00000340284.5

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119207 AN: 151970 Hom.: 46928 Cov.: 32

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.800

GnomAD4 exome AF: 0.775 AC: 606623 AN: 783178 Hom.: 236704 Cov.: 10 AF XY: 0.778 AC XY: 311804 AN XY: 401024

African (AFR) AF: 0.795 AC: 15029 AN: 18902

American (AMR) AF: 0.879 AC: 20314 AN: 23108

Ashkenazi Jewish (ASJ) AF: 0.811 AC: 13059 AN: 16102

East Asian (EAS) AF: 0.984 AC: 34353 AN: 34908

South Asian (SAS) AF: 0.843 AC: 47929 AN: 56824

European-Finnish (FIN) AF: 0.740 AC: 26931 AN: 36392

Middle Eastern (MID) AF: 0.816 AC: 3345 AN: 4098

European-Non Finnish (NFE) AF: 0.749 AC: 416418 AN: 555676

Other (OTH) AF: 0.787 AC: 29245 AN: 37168

GnomAD4 genome AF: 0.784 AC: 119272 AN: 152088 Hom.: 46949 Cov.: 32 AF XY: 0.788 AC XY: 58628 AN XY: 74364

African (AFR) AF: 0.794 AC: 32938 AN: 41498

American (AMR) AF: 0.838 AC: 12817 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.787 AC: 2732 AN: 3470

East Asian (EAS) AF: 0.988 AC: 5088 AN: 5150

South Asian (SAS) AF: 0.843 AC: 4067 AN: 4822

European-Finnish (FIN) AF: 0.747 AC: 7917 AN: 10602

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.750 AC: 50970 AN: 67934

Other (OTH) AF: 0.803 AC: 1696 AN: 2112

Alfa AF: 0.776 Hom.: 31506

Bravo AF: 0.794

Asia WGS AF: 0.900 AC: 3130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.80
PhyloP100		0.15
Mutation Taster		=99/1	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: rs1051013; hg19: chr9-116359339;