Variant 8-99987487-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000360863.11(RGS22):c.3151C>G(p.Leu1051Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000683 in 1,610,384 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00042 ( 2 hom., cov: 33)

Exomes 𝑓: 0.000032 ( 1 hom. )

Consequence

RGS22
ENST00000360863.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.63

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 Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS22	NM_015668.5 linkuse as main transcript	c.3151C>G	p.Leu1051Val	missense_variant	21/28	ENST00000360863.11	NP_056483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS22	ENST00000360863.11 linkuse as main transcript	c.3151C>G	p.Leu1051Val	missense_variant	21/28	1	NM_015668.5	ENSP00000354109	P3	Q8NE09-1
RGS22	ENST00000523437.5 linkuse as main transcript	c.3115C>G	p.Leu1039Val	missense_variant	21/28	1		ENSP00000428212	A2	Q8NE09-3
RGS22	ENST00000523287.5 linkuse as main transcript	c.2608C>G	p.Leu870Val	missense_variant	19/26	2		ENSP00000429382	A2
RGS22	ENST00000517769.5 linkuse as main transcript	n.1379C>G		non_coding_transcript_exon_variant	10/17	2

Frequencies

GnomAD3 genomes

AF:

0.000421

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

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:

0.00143

GnomAD3 exomes

AF:

0.0000565

AC:

AN:

248004

Hom.:

AF XY:

0.0000594

AC XY:

AN XY:

134662

show subpopulations

Gnomad AFR exome

AF:

0.000453

Gnomad AMR exome

AF:

0.0000879

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:

0.000665

GnomAD4 exome

AF:

0.0000315

AC:

AN:

1458152

Hom.:

Cov.:

AF XY:

0.0000317

AC XY:

AN XY:

725418

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000472

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.000316

GnomAD4 genome

AF:

0.000420

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00301

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:

0.00142

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.00107

ESP6500AA

AF:

0.000277

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000414

AC:

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

Dec 18, 2023

The c.3151C>G (p.L1051V) alteration is located in exon 21 (coding exon 21) of the RGS22 gene. This alteration results from a C to G substitution at nucleotide position 3151, causing the leucine (L) at amino acid position 1051 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

-0.40

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.029

T;T;T;.

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.81

T;T;T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.20

T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.5

M;.;.;.

MutationTaster

Benign

0.60

N;N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.6

N;.;N;N

REVEL

Benign

0.19

Sift

Benign

0.033

D;.;D;D

Sift4G

Uncertain

0.027

D;D;D;D

Polyphen

1.0

D;.;D;.

Vest4

0.56

MVP

0.65

MPC

0.34

ClinPred

0.16

GERP RS

6.0

Varity_R

0.19

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.27

Position offset: -29

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