Genetic Variant RGS19:p.Arg56Gln (chr20-64074527-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005873.3(RGS19):c.167G>A(p.Arg56Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000365 in 1,562,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00038 ( 0 hom. )

Consequence

RGS19
NM_005873.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.729

Publications

3 publications found

Variant links:

Genes affected

RGS19 (HGNC:13735): (regulator of G protein signaling 19) G proteins mediate a number of cellular processes. The protein encoded by this gene belongs to the RGS (regulators of G-protein signaling) family and specifically interacts with G protein, GAI3. This protein is a guanosine triphosphatase-activating protein that functions to down-regulate Galpha i/Galpha q-linked signaling. Alternatively spliced transcript variants encoding the same protein isoform have been found for this gene. [provided by RefSeq, Jul 2008]

RGS19 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014374703).

BS2

High AC in GnomAd4 at 37 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005873.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS19	NM_005873.3	MANE Select	c.167G>A	p.Arg56Gln	missense	Exon 4 of 6	NP_005864.1	P49795
	RGS19	NM_001039467.2		c.167G>A	p.Arg56Gln	missense	Exon 4 of 6	NP_001034556.1	P49795

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RGS19	ENST00000395042.2	TSL:1 MANE Select	c.167G>A	p.Arg56Gln	missense	Exon 4 of 6	ENSP00000378483.1	P49795
RGS19	ENST00000332298.9	TSL:1	c.167G>A	p.Arg56Gln	missense	Exon 4 of 6	ENSP00000333194.5	P49795
RGS19	ENST00000910389.1		c.209G>A	p.Arg70Gln	missense	Exon 4 of 6	ENSP00000580448.1

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000283

AC:

AN:

165850

AF XY:

0.000348

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000344

Gnomad ASJ exome

AF:

0.000472

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000484

Gnomad OTH exome

AF:

0.000447

GnomAD4 exome

AF:

0.000379

AC:

534

AN:

1410634

Hom.:

Cov.:

AF XY:

0.000354

AC XY:

247

AN XY:

697210

show subpopulations

African (AFR)

AF:

0.0000620

AC:

AN:

32246

American (AMR)

AF:

0.000347

AC:

AN:

37412

Ashkenazi Jewish (ASJ)

AF:

0.000515

AC:

AN:

25258

East Asian (EAS)

AF:

0.00

AC:

AN:

36788

South Asian (SAS)

AF:

0.00

AC:

AN:

80386

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48072

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.000453

AC:

492

AN:

1086342

Other (OTH)

AF:

0.000223

AC:

AN:

58426

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

110

137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

110

<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:

0.000243

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000485

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000328

Hom.:

Bravo

AF:

0.000264

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000483

AC:

ExAC

AF:

0.000269

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.21

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.68

M_CAP

Benign

0.033

MetaRNN

Benign

0.014

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.23

PhyloP100

0.73

PrimateAI

Benign

0.40

PROVEAN

Benign

1.2

REVEL

Benign

0.14

Sift

Benign

1.0

Sift4G

Benign

0.56

Polyphen

0.0

Vest4

0.16

MVP

0.44

MPC

0.59

ClinPred

0.043

GERP RS

2.7

Varity_R

0.023

gMVP

0.27

Mutation Taster

=96/4

polymorphism

(source)

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

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