Variant chr1-182648213-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001102450.3(RGS8):c.284C>T(p.Thr95Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00116 in 1,613,694 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0046 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00081 ( 6 hom. )

Consequence

RGS8
NM_001102450.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.92

Variant links:

Genes affected

RGS8 (HGNC:16810): (regulator of G protein signaling 8) This gene is a member of the regulator of G protein signaling (RGS) family and encodes a protein with a single RGS domain. Regulator of G protein signaling (RGS) proteins are regulatory and structural components of G protein-coupled receptor complexes. They accelerate transit through the cycle of GTP binding and hydrolysis to GDP, thereby terminating signal transduction, but paradoxically, also accelerate receptor-stimulated activation. [provided by RefSeq, Jul 2008]

RGS8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0060186684).

BP6

Variant 1-182648213-G-A is Benign according to our data. Variant chr1-182648213-G-A is described in ClinVar as [Benign]. Clinvar id is 3257702.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 694 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS8	NM_001102450.3 linkuse as main transcript	c.284C>T	p.Thr95Ile	missense_variant	7/8	ENST00000515211.2	NP_001095920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS8	ENST00000515211.2 linkuse as main transcript	c.284C>T	p.Thr95Ile	missense_variant	7/8	4	NM_001102450.3	ENSP00000511884	P1	P57771-1

Frequencies

GnomAD3 genomes

AF:

0.00454

AC:

690

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000662

Gnomad OTH

AF:

0.00623

GnomAD3 exomes

AF:

0.00164

AC:

412

AN:

251028

Hom.:

AF XY:

0.00140

AC XY:

190

AN XY:

135668

show subpopulations

Gnomad AFR exome

AF:

0.0141

Gnomad AMR exome

AF:

0.00245

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000651

Gnomad OTH exome

AF:

0.00213

GnomAD4 exome

AF:

0.000806

AC:

1178

AN:

1461472

Hom.:

Cov.:

AF XY:

0.000784

AC XY:

570

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.0117

Gnomad4 AMR exome

AF:

0.00257

Gnomad4 ASJ exome

AF:

0.00122

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000581

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000443

Gnomad4 OTH exome

AF:

0.00192

GnomAD4 genome

AF:

0.00456

AC:

694

AN:

152222

Hom.:

Cov.:

AF XY:

0.00426

AC XY:

317

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0134

Gnomad4 AMR

AF:

0.00464

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000662

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00127

Hom.:

Bravo

AF:

0.00534

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.0116

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00181

AC:

220

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000819

EpiControl

AF:

0.000890

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

RGS8: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.024

.;T;T;T

Eigen

Benign

-0.26

Eigen_PC

Benign

0.0014

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

T;.;.;T

MetaRNN

Benign

0.0060

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.33

.;N;N;N

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

0.25

N;N;N;N

REVEL

Benign

0.13

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.029

B;B;B;B

Vest4

0.17

MVP

0.043

MPC

0.51

ClinPred

0.014

GERP RS

5.5

Varity_R

0.27

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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