chr9-113565180-C-T

Position:

• chr9-113565180-C-T

Variant summary

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

The NM_001322215.2(RGS3):​c.-127C>T 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 0.0551 in 1,230,526 control chromosomes in the GnomAD database, including 2,112 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 0.039 (158 hom., cov: 32)
  • Exomes 𝑓: 0.057 (1954 hom.)
• Consequence: RGS3 NM_001322215.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

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]

RGS3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS3	NM_001394167.1	c.1702-18270C>T		intron_variant		ENST00000695401.1	NP_001381096.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS3	ENST00000695401.1	c.1702-18270C>T		intron_variant			NM_001394167.1	ENSP00000511882.1

Frequencies

GnomAD3 genomes AF: 0.0393 AC: 5981 AN: 152066 Hom.: 158 Cov.: 32

Gnomad AFR AF: 0.00918

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0215

Gnomad ASJ AF: 0.0901

Gnomad EAS AF: 0.0161

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0420

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0560

Gnomad OTH AF: 0.0364

GnomAD4 exome AF: 0.0573 AC: 61772 AN: 1078342 Hom.: 1954 Cov.: 30 AF XY: 0.0583 AC XY: 30495 AN XY: 522638

Gnomad4 AFR exome AF: 0.00759

Gnomad4 AMR exome AF: 0.0168

Gnomad4 ASJ exome AF: 0.0833

Gnomad4 EAS exome AF: 0.0139

Gnomad4 SAS exome AF: 0.0957

Gnomad4 FIN exome AF: 0.0507

Gnomad4 NFE exome AF: 0.0570

Gnomad4 OTH exome AF: 0.0577

GnomAD4 genome AF: 0.0393 AC: 5978 AN: 152184 Hom.: 158 Cov.: 32 AF XY: 0.0389 AC XY: 2891 AN XY: 74394

Gnomad4 AFR AF: 0.00915

Gnomad4 AMR AF: 0.0214

Gnomad4 ASJ AF: 0.0901

Gnomad4 EAS AF: 0.0161

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.0420

Gnomad4 NFE AF: 0.0560

Gnomad4 OTH AF: 0.0356

Alfa AF: 0.0448 Hom.: 81

Bravo AF: 0.0345

Asia WGS AF: 0.0530 AC: 184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.75

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: rs3747813; hg19: chr9-116327460;