chr9-113462048-C-G

Variant names:

• chr9-113462048-C-G
• rs781339051
• ENST00000350696.9:c.262C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144488.8(RGS3):​c.-51C>G 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: 31)
• Consequence: RGS3 NM_144488.8 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1050784).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144488.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS3	NM_144488.8		c.-51C>G		5_prime_UTR	Exon 4 of 26	NP_652759.4	P49796-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS3	ENST00000350696.9	TSL:5	c.262C>G	p.Leu88Val	missense	Exon 3 of 25	ENSP00000259406.7	P49796-3
	RGS3	ENST00000374140.6	TSL:2	c.262C>G	p.Leu88Val	missense	Exon 4 of 26	ENSP00000363255.2	P49796-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	4.5
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.22
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.055
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.73	P
Vest4		0.23
MutPred		0.27		Loss of sheet (P = 0.0315)
MVP		0.29
MPC		0.20
ClinPred		0.10	T
GERP RS		1.6
Varity_R		0.12
gMVP		0.031
Mutation Taster		=98/2	polymorphism

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: rs781339051; hg19: chr9-116224328;