1-182648141-C-A

Variant names:

• chr1-182648141-C-A
• rs760003150
• NM_001102450.3:c.356G>T

Variant summary

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

The NM_001102450.3(RGS8):​c.356G>T​(p.Arg119Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R119Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RGS8 NM_001102450.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.31
• Publications: 0 publications found

Genes affected

RGS8 (HGNC:16810): (regulator of G protein signaling 8) This gene is a member of the regulator of G protein signaling (RGS) family and encodes a protein with a single RGS domain. Regulator of G protein signaling (RGS) proteins are regulatory and structural components of G protein-coupled receptor complexes. They accelerate transit through the cycle of GTP binding and hydrolysis to GDP, thereby terminating signal transduction, but paradoxically, also accelerate receptor-stimulated activation. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001102450.3. 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
	RGS8	NM_001102450.3	MANE Select	c.356G>T	p.Arg119Leu	missense	Exon 7 of 8	NP_001095920.1	P57771-1
	RGS8	NM_033345.4		c.410G>T	p.Arg137Leu	missense	Exon 6 of 7	NP_203131.1	P57771-2
	RGS8	NM_001369564.2		c.356G>T	p.Arg119Leu	missense	Exon 5 of 6	NP_001356493.1	P57771-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS8	ENST00000515211.2	TSL:4 MANE Select	c.356G>T	p.Arg119Leu	missense	Exon 7 of 8	ENSP00000511884.1	P57771-1
	RGS8	ENST00000258302.8	TSL:1	c.410G>T	p.Arg137Leu	missense	Exon 5 of 6	ENSP00000258302.4	P57771-2
	RGS8	ENST00000367557.8	TSL:1	c.356G>T	p.Arg119Leu	missense	Exon 6 of 7	ENSP00000356528.4	P57771-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.3
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.95	P
Vest4		0.81
MutPred		0.67		Loss of solvent accessibility (P = 0.0098)
MVP		0.30
MPC		0.61
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.78
gMVP		0.65
Mutation Taster		=41/59	disease causing

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: rs760003150; hg19: chr1-182617276;