Variant 8-99999276-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015668.5(RGS22):c.2935C>T(p.Arg979Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,164 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

RGS22
NM_015668.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.08

Variant links:

Genes affected

RGS22 (HGNC:24499): (regulator of G protein signaling 22) Enables G-protein alpha-subunit binding activity. Predicted to be involved in negative regulation of signal transduction. Located in actin cytoskeleton; cytosol; and fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

RGS22 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS22	NM_015668.5 linkuse as main transcript	c.2935C>T	p.Arg979Cys	missense_variant	19/28	ENST00000360863.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS22	ENST00000360863.11 linkuse as main transcript	c.2935C>T	p.Arg979Cys	missense_variant	19/28	1	NM_015668.5	P3	Q8NE09-1
RGS22	ENST00000523437.5 linkuse as main transcript	c.2899C>T	p.Arg967Cys	missense_variant	19/28	1		A2	Q8NE09-3
RGS22	ENST00000523287.5 linkuse as main transcript	c.2392C>T	p.Arg798Cys	missense_variant	17/26	2		A2
RGS22	ENST00000517769.5 linkuse as main transcript	n.1163C>T		non_coding_transcript_exon_variant	8/17	2

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151824

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000241

AC:

AN:

248656

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

134884

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000112

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461340

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151824

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74142

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000331

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

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

Sep 22, 2022

The c.2935C>T (p.R979C) alteration is located in exon 19 (coding exon 19) of the RGS22 gene. This alteration results from a C to T substitution at nucleotide position 2935, causing the arginine (R) at amino acid position 979 to be replaced by a cysteine (C). 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

Pathogenic

0.80

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.30

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.15

T;T;T;.

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

D;D;D;D

M_CAP

Uncertain

0.099

MetaRNN

Uncertain

0.71

D;D;D;D

MetaSVM

Benign

-0.51

MutationAssessor

Uncertain

2.6

M;.;.;.

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-4.4

D;.;D;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.0010

D;.;D;D

Sift4G

Uncertain

0.0030

D;D;D;D

Polyphen

1.0

D;.;D;.

Vest4

0.61

MutPred

0.46

Loss of MoRF binding (P = 0.0224);.;.;.;

MVP

0.72

MPC

0.40

ClinPred

0.99

GERP RS

4.9

Varity_R

0.41

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.21

Position offset: -14

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