Variant 8-99962943-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015668.5(RGS22):c.3651A>G(p.Leu1217=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00495 in 1,596,860 control chromosomes in the GnomAD database, including 298 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 157 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 141 hom. )

Consequence

RGS22
NM_015668.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.359

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 Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 8-99962943-T-C is Benign according to our data. Variant chr8-99962943-T-C is described in ClinVar as [Benign]. Clinvar id is 776366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.359 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS22	NM_015668.5 linkuse as main transcript	c.3651A>G	p.Leu1217=	synonymous_variant	25/28	ENST00000360863.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS22	ENST00000360863.11 linkuse as main transcript	c.3651A>G	p.Leu1217=	synonymous_variant	25/28	1	NM_015668.5	P3	Q8NE09-1

Frequencies

GnomAD3 genomes

AF:

0.0269

AC:

4089

AN:

152182

Hom.:

157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0918

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0141

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.00699

AC:

1612

AN:

230740

Hom.:

AF XY:

0.00557

AC XY:

697

AN XY:

125158

show subpopulations

Gnomad AFR exome

AF:

0.0933

Gnomad AMR exome

AF:

0.00521

Gnomad ASJ exome

AF:

0.000997

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000388

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000222

Gnomad OTH exome

AF:

0.00399

GnomAD4 exome

AF:

0.00264

AC:

3816

AN:

1444560

Hom.:

141

Cov.:

AF XY:

0.00237

AC XY:

1699

AN XY:

717952

show subpopulations

Gnomad4 AFR exome

AF:

0.0933

Gnomad4 AMR exome

AF:

0.00567

Gnomad4 ASJ exome

AF:

0.00130

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000111

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000164

Gnomad4 OTH exome

AF:

0.00590

GnomAD4 genome

AF:

0.0269

AC:

4096

AN:

152300

Hom.:

157

Cov.:

AF XY:

0.0263

AC XY:

1958

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0917

Gnomad4 AMR

AF:

0.0141

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.0122

Hom.:

Bravo

AF:

0.0304

Asia WGS

AF:

0.00636

AC:

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.5

DANN

Benign

0.72

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