Variant 8-53958454-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_170587.4(RGS20):c.1163C>T(p.Ala388Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000172 in 1,453,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

RGS20
NM_170587.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.38

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18090698).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS20	NM_170587.4 linkuse as main transcript	c.1163C>T	p.Ala388Val	missense_variant	6/6	ENST00000297313.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS20	ENST00000297313.8 linkuse as main transcript	c.1163C>T	p.Ala388Val	missense_variant	6/6	1	NM_170587.4		O76081-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000617

AC:

AN:

162182

Hom.:

AF XY:

0.0000112

AC XY:

AN XY:

89586

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000640

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:

0.0000169

AC:

AN:

1301856

Hom.:

Cov.:

AF XY:

0.00000622

AC XY:

AN XY:

642702

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000378

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:

0.0000194

Gnomad4 OTH exome

AF:

0.0000189

GnomAD4 genome

AF:

0.0000197

AC:

AN:

151966

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2023

The c.1163C>T (p.A388V) alteration is located in exon 6 (coding exon 6) of the RGS20 gene. This alteration results from a C to T substitution at nucleotide position 1163, causing the alanine (A) at amino acid position 388 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

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.28

T;.;.;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.89

D;D;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.18

T;T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.8

L;.;.;.

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.8

D;D;D;D

REVEL

Benign

0.11

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

0.95

P;P;.;P

Vest4

0.094

MutPred

0.25

Gain of methylation at K384 (P = 0.1089);.;.;.;

MVP

0.76

MPC

0.54

ClinPred

0.96

GERP RS

5.2

Varity_R

0.30

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