9-113594236-A-C

Variant names:

• chr9-113594236-A-C
• rs12341266
• ENST00000620489.1:c.-41A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000620489.1(RGS3):​c.-41A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: RGS3 ENST00000620489.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234
• Publications: 31 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0617719).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000620489.1. 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.2745-194A>C		intron	N/A	NP_001381096.1
	RGS3	NM_144489.4		c.-41A>C		5_prime_UTR	Exon 1 of 5	NP_652760.3
	RGS3	NM_001276262.2		c.-61A>C		5_prime_UTR	Exon 1 of 5	NP_001263191.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS3	ENST00000620489.1	TSL:1	c.-41A>C		5_prime_UTR	Exon 1 of 5	ENSP00000479017.1
	RGS3	ENST00000695401.1	MANE Select	c.2745-194A>C		intron	N/A	ENSP00000511882.1
	RGS3	ENST00000343817.9	TSL:1	c.2238-194A>C		intron	N/A	ENSP00000340284.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 70

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 46806

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	8.0
DANN	Benign	0.39
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.23
PROVEAN	Benign	0.49	N
REVEL	Benign	0.067
Sift	Benign	0.25	T
Sift4G	Benign	0.41	T
Vest4		0.047
MutPred		0.46		Gain of glycosylation at Y106 (P = 0.0218)
MVP		0.076
ClinPred		0.13	T
GERP RS		-1.2
PromoterAI		0.059	Neutral

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: rs12341266; hg19: chr9-116356516;