Variant 8-53939667-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_170587.4(RGS20):c.602G>A(p.Gly201Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,581,944 control chromosomes in the GnomAD database, including 2 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000094 ( 1 hom. )

Consequence

RGS20
NM_170587.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.56

Variant links:

Genes affected

RGS20 (HGNC:14600): (regulator of G protein signaling 20) The protein encoded by this gene belongs to the family of regulator of G protein signaling (RGS) proteins, which are regulatory and structural components of G protein-coupled receptor complexes. RGS proteins inhibit signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound forms. This protein selectively binds to G(z)-alpha and G(alpha)-i2 subunits, and regulates their signaling activities. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

RGS20 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0056562126).

BP6

Variant 8-53939667-G-A is Benign according to our data. Variant chr8-53939667-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 754436.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 166 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS20	NM_170587.4 link	c.602G>A	p.Gly201Glu	missense_variant	3/6	ENST00000297313.8	NP_733466.1	O76081-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS20	ENST00000297313.8 link	c.602G>A	p.Gly201Glu	missense_variant	3/6	1	NM_170587.4	ENSP00000297313.3		O76081-1
RGS20	ENST00000276500.4 link	c.161G>A	p.Gly54Glu	missense_variant	2/5	1		ENSP00000276500.4		O76081-6

Frequencies

GnomAD3 genomes

AF:

0.00109

AC:

166

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00381

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000226

AC:

AN:

194490

Hom.:

AF XY:

0.000116

AC XY:

AN XY:

103534

show subpopulations

Gnomad AFR exome

AF:

0.00346

Gnomad AMR exome

AF:

0.000111

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000944

AC:

135

AN:

1429648

Hom.:

Cov.:

AF XY:

0.0000721

AC XY:

AN XY:

707590

show subpopulations

Gnomad4 AFR exome

AF:

0.00371

Gnomad4 AMR exome

AF:

0.0000780

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:

9.12e-7

Gnomad4 OTH exome

AF:

0.000135

GnomAD4 genome

AF:

0.00109

AC:

166

AN:

152296

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00380

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000138

Hom.:

Bravo

AF:

0.00116

ESP6500AA

AF:

0.00205

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000218

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.25

T;.;.

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.59

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.0057

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-2.3

N;N;N

REVEL

Benign

0.085

Sift

Benign

0.11

T;D;T

Sift4G

Benign

0.13

T;T;T

Polyphen

0.021

B;B;B

Vest4

0.23

MVP

0.70

MPC

0.68

ClinPred

0.035

GERP RS

3.1

Varity_R

0.088

gMVP

0.28

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