1-182671676-T-C

Position:

• chr1-182671676-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000258302.8(RGS8):​c.61A>G​(p.Met21Val) 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. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RGS8 ENST00000258302.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.04

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.072313994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS8	NM_001102450.3	c.-123A>G		5_prime_UTR_variant	3/8	ENST00000515211.2	NP_001095920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS8	ENST00000515211.2	c.-123A>G		5_prime_UTR_variant	3/8	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

Feb 23, 2023

The c.61A>G (p.M21V) alteration is located in exon 2 (coding exon 2) of the RGS8 gene. This alteration results from a A to G substitution at nucleotide position 61, causing the methionine (M) at amino acid position 21 to be replaced by a valine (V). 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
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	20
DANN	Benign	0.93
Eigen	Benign	-0.15
Eigen_PC	Benign	0.012
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.14
Sift	Benign	0.79	T
Sift4G	Benign	0.54	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.15		Gain of phosphorylation at T23 (P = 0.088);
MVP		0.27
MPC		0.46
ClinPred		0.75	D
GERP RS		4.2
gMVP		0.23

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-182640811;