ENST00000488620.5:n.105C>T

Variant names:

• chr9-113565180-C-T
• rs3747813
• ENST00000488620.5:n.105C>T

Variant summary

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

The ENST00000488620.5(RGS3):​n.105C>T variant causes a non coding transcript exon 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 ENST00000488620.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 7 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0929 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000488620.5. 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.1702-18270C>T		intron	N/A	NP_001381096.1
	RGS3	NM_001322215.2		c.-127C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	NP_001309144.1
	RGS3	NM_001351526.2		c.-565C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	NP_001338455.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS3	ENST00000488620.5	TSL:1	n.105C>T		non_coding_transcript_exon	Exon 1 of 3
	RGS3	ENST00000695401.1	MANE Select	c.1702-18270C>T		intron	N/A	ENSP00000511882.1
	RGS3	ENST00000343817.9	TSL:1	c.1195-18270C>T		intron	N/A	ENSP00000340284.5

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

African (AFR) AF: 0.00759 AC: 171 AN: 22520

American (AMR) AF: 0.0168 AC: 351 AN: 20850

Ashkenazi Jewish (ASJ) AF: 0.0833 AC: 970 AN: 11638

East Asian (EAS) AF: 0.0139 AC: 172 AN: 12358

South Asian (SAS) AF: 0.0957 AC: 6285 AN: 65698

European-Finnish (FIN) AF: 0.0507 AC: 534 AN: 10524

Middle Eastern (MID) AF: 0.0601 AC: 234 AN: 3892

European-Non Finnish (NFE) AF: 0.0570 AC: 50808 AN: 891918

Other (OTH) AF: 0.0577 AC: 2247 AN: 38944

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

African (AFR) AF: 0.00915 AC: 380 AN: 41538

American (AMR) AF: 0.0214 AC: 328 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0901 AC: 313 AN: 3472

East Asian (EAS) AF: 0.0161 AC: 83 AN: 5152

South Asian (SAS) AF: 0.100 AC: 483 AN: 4814

European-Finnish (FIN) AF: 0.0420 AC: 445 AN: 10598

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0560 AC: 3808 AN: 68002

Other (OTH) AF: 0.0356 AC: 75 AN: 2108

Alfa AF: 0.0431 Hom.: 97

Bravo AF: 0.0345

Asia WGS AF: 0.0530 AC: 184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.75
PhyloP100		-1.9
PromoterAI		-0.097	Neutral
Mutation Taster		=294/6	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: rs3747813; hg19: chr9-116327460;