Genetic Variant RGS13:p.Arg3Lys (chr1-192644342-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002927.5(RGS13):c.8G>A(p.Arg3Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,457,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

RGS13
NM_002927.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.17

Variant links:

Genes affected

RGS13 (HGNC:9995): (regulator of G protein signaling 13) The protein encoded by this gene is a member of the regulator of G protein signaling (RGS) family. RGS family members share similarity with S. cerevisiae SST2 and C. elegans egl-10 proteins, which contain a characteristic conserved RGS domain. RGS proteins accelerate GTPase activity of G protein alpha-subunits, thereby driving G protein into their inactive GDP-bound form, thus negatively regulating G protein signaling. RGS proteins have been implicated in the fine tuning of a variety of cellular events in response to G protein-coupled receptor activation. The biological function of this gene, however, is unknown. Two transcript variants encoding the same isoform exist. [provided by RefSeq, Jul 2008]

RGS13 links:

ENSG00000285280 (HGNC:49018): (RSG2 antisense RNA 1)

ENSG00000285280 links:

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ACMG classification

Classification made for transcript

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=0.120293915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS13	NM_002927.5 link	c.8G>A	p.Arg3Lys	missense_variant	Exon 4 of 7	ENST00000391995.7	NP_002918.1	O14921
RGS13	NM_144766.3 link	c.8G>A	p.Arg3Lys	missense_variant	Exon 3 of 6		NP_658912.1	O14921

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS13	ENST00000391995.7 link	c.8G>A	p.Arg3Lys	missense_variant	Exon 4 of 7	1	NM_002927.5	ENSP00000375853.2		O14921

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000800

AC:

AN:

250112

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135176

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1457820

Hom.:

Cov.:

AF XY:

0.0000262

AC XY:

AN XY:

725348

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000424

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.8G>A (p.R3K) alteration is located in exon 4 (coding exon 1) of the RGS13 gene. This alteration results from a G to A substitution at nucleotide position 8, causing the arginine (R) at amino acid position 3 to be replaced by a lysine (K). 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

0.098

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-0.019

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.43

T;.

M_CAP

Benign

0.0055

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.63

N;N

REVEL

Benign

0.046

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.43

T;T

Polyphen

0.23

B;B

Vest4

0.31

MutPred

0.32

Gain of methylation at R3 (P = 0.0025);Gain of methylation at R3 (P = 0.0025);

MVP

0.70

MPC

0.032

ClinPred

0.44

GERP RS

4.6

Varity_R

0.24

gMVP

0.32

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over