Variant 8-100038971-T-C 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.2126A>G(p.Gln709Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000744 in 1,612,530 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

RGS22
NM_015668.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.94

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:

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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.2126A>G	p.Gln709Arg	missense_variant	14/28	ENST00000360863.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS22	ENST00000360863.11 linkuse as main transcript	c.2126A>G	p.Gln709Arg	missense_variant	14/28	1	NM_015668.5	P3	Q8NE09-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1460340

Hom.:

Cov.:

AF XY:

0.00000964

AC XY:

AN XY:

726458

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000986

Hom.:

Bravo

AF:

0.0000227

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

Oct 16, 2023

The c.2126A>G (p.Q709R) alteration is located in exon 14 (coding exon 14) of the RGS22 gene. This alteration results from a A to G substitution at nucleotide position 2126, causing the glutamine (Q) at amino acid position 709 to be replaced by an arginine (R). 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

0.14

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.34

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.013

T;T;T;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.83

T;T;T;T

M_CAP

Benign

0.042

MetaRNN

Uncertain

0.57

D;D;D;D

MetaSVM

Benign

-0.58

MutationAssessor

Uncertain

2.2

M;.;.;.

MutationTaster

Benign

0.50

D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.9

N;.;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.025

D;.;D;D

Sift4G

Uncertain

0.034

D;D;D;D

Polyphen

1.0

D;.;D;.

Vest4

0.55

MVP

0.56

MPC

0.33

ClinPred

0.93

GERP RS

5.2

Varity_R

0.31

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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