Variant 8-53879382-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_170587.4(RGS20):c.290C>A(p.Ala97Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000142 in 1,611,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

RGS20
NM_170587.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0700

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024302661).

BS2

High AC in GnomAd4 at 78 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS20	NM_170587.4 link	c.290C>A	p.Ala97Asp	missense_variant	2/6	ENST00000297313.8	NP_733466.1	O76081-1
RGS20	NM_001286673.2 link	c.165+27318C>A		intron_variant			NP_001273602.1	O76081-2
RGS20	NM_001286675.2 link	c.35+27318C>A		intron_variant			NP_001273604.1	O76081-3
RGS20	NM_001286674.2 link	c.35+27318C>A		intron_variant			NP_001273603.1	O76081-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RGS20	ENST00000297313.8 link	c.290C>A	p.Ala97Asp	missense_variant	2/6	1	NM_170587.4	ENSP00000297313.3	O76081-1
RGS20	ENST00000344277.10 link	c.165+27318C>A		intron_variant		1		ENSP00000344630.6	O76081-2
RGS20	ENST00000517659.5 link	n.165+27318C>A		intron_variant		1		ENSP00000428795.1	E5RGA3
RGS20	ENST00000523280.1 link	n.165+27318C>A		intron_variant		1		ENSP00000429897.1	E5RH54

Frequencies

GnomAD3 genomes

AF:

0.000500

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000187

AC:

AN:

246362

Hom.:

AF XY:

0.000164

AC XY:

AN XY:

134070

show subpopulations

Gnomad AFR exome

AF:

0.00118

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00120

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000894

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000103

AC:

151

AN:

1459136

Hom.:

Cov.:

AF XY:

0.0000992

AC XY:

AN XY:

725984

show subpopulations

Gnomad4 AFR exome

AF:

0.00137

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00126

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.000547

GnomAD4 genome

AF:

0.000512

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000356

Hom.:

Bravo

AF:

0.000552

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000231

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000237

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

Feb 27, 2023

The c.290C>A (p.A97D) alteration is located in exon 2 (coding exon 2) of the RGS20 gene. This alteration results from a C to A substitution at nucleotide position 290, causing the alanine (A) at amino acid position 97 to be replaced by an aspartic acid (D). 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

0.10

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.22

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.44

M_CAP

Benign

0.020

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.81

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.88

REVEL

Benign

0.15

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.017

Polyphen

0.94

Vest4

0.34

MVP

0.78

MPC

0.88

ClinPred

0.066

GERP RS

3.5

Varity_R

0.39

gMVP

0.25

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