1-182646876-G-C

Variant names:

• chr1-182646876-G-C
• rs75416974
• NM_001102450.3:c.402C>G

Variant summary

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

The NM_001102450.3(RGS8):​c.402C>G​(p.Asn134Lys) variant causes a missense 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RGS8 NM_001102450.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2601015).

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.402C>G	p.Asn134Lys	missense	Exon 8 of 8	NP_001095920.1	P57771-1
	RGS8	NM_033345.4		c.456C>G	p.Asn152Lys	missense	Exon 7 of 7	NP_203131.1	P57771-2
	RGS8	NM_001369564.2		c.402C>G	p.Asn134Lys	missense	Exon 6 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.402C>G	p.Asn134Lys	missense	Exon 8 of 8	ENSP00000511884.1	P57771-1
	RGS8	ENST00000258302.8	TSL:1	c.456C>G	p.Asn152Lys	missense	Exon 6 of 6	ENSP00000258302.4	P57771-2
	RGS8	ENST00000367557.8	TSL:1	c.402C>G	p.Asn134Lys	missense	Exon 7 of 7	ENSP00000356528.4	P57771-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	Uncertain	0.56
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.099
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.9
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.12
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.015	D
Polyphen		0.96	P
Vest4		0.16
MutPred		0.66		Gain of ubiquitination at N134 (P = 0.0155)
MVP		0.21
MPC		1.4
ClinPred		0.99	D
GERP RS		3.4
Varity_R		0.87
gMVP		0.29
Mutation Taster		=49/51	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: rs75416974; hg19: chr1-182616011;