Genetic Variant RGS8:p.Thr95Ile (chr1-182648213-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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

Publications

6 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 3257702.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 694 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001102450.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RGS8	NM_001102450.3	MANE Select	c.284C>T	p.Thr95Ile	missense	Exon 7 of 8	NP_001095920.1	P57771-1
RGS8	NM_033345.4		c.338C>T	p.Thr113Ile	missense	Exon 6 of 7	NP_203131.1	P57771-2
RGS8	NM_001369564.2		c.284C>T	p.Thr95Ile	missense	Exon 5 of 6	NP_001356493.1	P57771-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RGS8	ENST00000515211.2	TSL:4 MANE Select	c.284C>T	p.Thr95Ile	missense	Exon 7 of 8	ENSP00000511884.1	P57771-1
RGS8	ENST00000258302.8	TSL:1	c.338C>T	p.Thr113Ile	missense	Exon 5 of 6	ENSP00000258302.4	P57771-2
RGS8	ENST00000367557.8	TSL:1	c.284C>T	p.Thr95Ile	missense	Exon 6 of 7	ENSP00000356528.4	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

GnomAD2 exomes

AF:

0.00164

AC:

412

AN:

251028

AF XY:

0.00140

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 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

African (AFR)

AF:

0.0117

AC:

392

AN:

33472

American (AMR)

AF:

0.00257

AC:

115

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.00122

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.0000581

AC:

AN:

86130

European-Finnish (FIN)

AF:

0.0000562

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00399

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000443

AC:

492

AN:

1111814

Other (OTH)

AF:

0.00192

AC:

116

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

133

200

266

333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00456

AC:

694

AN:

152222

Hom.:

Cov.:

AF XY:

0.00426

AC XY:

317

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0134

AC:

558

AN:

41536

American (AMR)

AF:

0.00464

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000662

AC:

AN:

68012

Other (OTH)

AF:

0.00616

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

130

162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00209

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.024

Eigen

Benign

-0.26

Eigen_PC

Benign

0.0014

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

MetaRNN

Benign

0.0060

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.33

PhyloP100

4.9

PrimateAI

Uncertain

0.70

PROVEAN

Benign

0.25

REVEL

Benign

0.13

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.029

Vest4

0.17

MVP

0.043

MPC

0.51

ClinPred

0.014

GERP RS

5.5

Varity_R

0.27

gMVP

0.37

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over