8-53879381-G-A

Position:

chr8-53879381-G-A

Variant summary

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

The NM_170587.4(RGS20):c.289G>A(p.Ala97Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,611,056 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A97D) has been classified 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: 0.432

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00989908).

BS2

High AC in GnomAd4 at 78 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RGS20	NM_170587.4 linkuse as main transcript	c.289G>A	p.Ala97Thr	missense_variant	2/6	ENST00000297313.8
RGS20	NM_001286673.2 linkuse as main transcript	c.165+27317G>A		intron_variant
RGS20	NM_001286674.2 linkuse as main transcript	c.35+27317G>A		intron_variant
RGS20	NM_001286675.2 linkuse as main transcript	c.35+27317G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	UniProt
RGS20	ENST00000297313.8 linkuse as main transcript	c.289G>A	p.Ala97Thr	missense_variant	2/6	1	NM_170587.4	O76081-1
RGS20	ENST00000344277.10 linkuse as main transcript	c.165+27317G>A		intron_variant		1		O76081-2
RGS20	ENST00000517659.5 linkuse as main transcript	c.165+27317G>A		intron_variant, NMD_transcript_variant		1
RGS20	ENST00000523280.1 linkuse as main transcript	c.165+27317G>A		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.000500

AC:

AN:

151988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

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:

0.0000883

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000187

AC:

AN:

246132

Hom.:

AF XY:

0.000157

AC XY:

AN XY:

133988

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:

0.00

Gnomad FIN exome

AF:

0.0000503

Gnomad NFE exome

AF:

0.0000894

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000102

AC:

149

AN:

1458954

Hom.:

Cov.:

AF XY:

0.0000964

AC XY:

AN XY:

725890

show subpopulations

Gnomad4 AFR exome

AF:

0.00138

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00126

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000197

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.000547

GnomAD4 genome

AF:

0.000513

AC:

AN:

152102

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

74376

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:

0.0000883

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000146

Hom.:

Bravo

AF:

0.000548

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.289G>A (p.A97T) alteration is located in exon 2 (coding exon 2) of the RGS20 gene. This alteration results from a G to A substitution at nucleotide position 289, causing the alanine (A) at amino acid position 97 to be replaced by a threonine (T). 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

0.079

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.63

CADD

Benign

9.1

DANN

Uncertain

0.98

DEOGEN2

Benign

0.21

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.46

M_CAP

Benign

0.012

MetaRNN

Benign

0.0099

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.56

REVEL

Benign

0.066

Sift

Benign

0.091

Sift4G

Benign

0.23

Polyphen

0.029

Vest4

0.15

MVP

0.62

MPC

0.45

ClinPred

0.0061

GERP RS

1.6

Varity_R

0.054

gMVP

0.12

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