Genetic Variant GPR20:p.Arg233His (chr8-141357226-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005293.3(GPR20):c.698G>A(p.Arg233His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000424 in 1,557,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R233C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

GPR20
NM_005293.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.54

Publications

0 publications found

Variant links:

Genes affected

GPR20 (HGNC:4475): (G protein-coupled receptor 20) Enables G protein-coupled receptor activity. Predicted to be involved in positive regulation of Rho protein signal transduction and positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway. Located in cytosol and plasma membrane. Is integral component of plasma membrane. Part of receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

GPR20 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.042962074).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005293.3. 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
	GPR20	NM_005293.3	MANE Select	c.698G>A	p.Arg233His	missense	Exon 2 of 2	NP_005284.2	Q99678

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPR20	ENST00000377741.4	TSL:3 MANE Select	c.698G>A	p.Arg233His	missense	Exon 2 of 2	ENSP00000366970.3	Q99678
GPR20	ENST00000887272.1		c.698G>A	p.Arg233His	missense	Exon 2 of 2	ENSP00000557331.1
GPR20	ENST00000887273.1		c.698G>A	p.Arg233His	missense	Exon 2 of 2	ENSP00000557332.1

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000874

AC:

AN:

160176

AF XY:

0.0000805

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000150

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000242

AC:

AN:

1405416

Hom.:

Cov.:

AF XY:

0.0000230

AC XY:

AN XY:

695288

show subpopulations

African (AFR)

AF:

0.000807

AC:

AN:

32220

American (AMR)

AF:

0.00

AC:

AN:

36904

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25314

East Asian (EAS)

AF:

0.00

AC:

AN:

36750

South Asian (SAS)

AF:

0.00

AC:

AN:

81450

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41780

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.00000644

AC:

AN:

1086808

Other (OTH)

AF:

0.0000171

AC:

AN:

58476

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000210

AC:

AN:

152366

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.000770

AC:

AN:

41582

American (AMR)

AF:

0.00

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

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:

0.000654

Hom.:

Bravo

AF:

0.000215

ESP6500AA

AF:

0.000696

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000618

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

0.091

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.038

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.80

M_CAP

Benign

0.073

MetaRNN

Benign

0.043

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.6

PhyloP100

1.5

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.4

REVEL

Benign

0.24

Sift

Uncertain

0.015

Sift4G

Uncertain

0.021

Polyphen

1.0

Vest4

0.17

MVP

0.60

MPC

0.57

ClinPred

0.13

GERP RS

3.9

Varity_R

0.31

gMVP

0.44

Mutation Taster

=84/16

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

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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