chr1-182666938-G-C

Position:

• chr1-182666938-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001102450.3(RGS8):​c.62C>G​(p.Ser21Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RGS8 NM_001102450.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.79

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS8	NM_001102450.3	c.62C>G	p.Ser21Cys	missense_variant	5/8	ENST00000515211.2	NP_001095920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS8	ENST00000515211.2	c.62C>G	p.Ser21Cys	missense_variant	5/8	4	NM_001102450.3	ENSP00000511884	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 01, 2024

The c.116C>G (p.S39C) alteration is located in exon 3 (coding exon 3) of the RGS8 gene. This alteration results from a C to G substitution at nucleotide position 116, causing the serine (S) at amino acid position 39 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Uncertain	0.069	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.056	.;T;T;T;.
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D;.;.;D;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.43	T;T;T;T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.1	.;M;M;M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.2	N;N;N;N;D
REVEL	Benign	0.19
Sift	Uncertain	0.011	D;D;D;D;D
Sift4G	Uncertain	0.037	D;D;D;D;D
Polyphen		1.0	D;D;D;D;.
Vest4		0.51
MutPred		0.33		.;Loss of phosphorylation at S21 (P = 0.0362);Loss of phosphorylation at S21 (P = 0.0362);Loss of phosphorylation at S21 (P = 0.0362);Loss of phosphorylation at S21 (P = 0.0362);
MVP		0.19
MPC		1.3
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.26
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-182636073;