Genetic Variant GPR20:p.Ala347Thr (chr8-141356885-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005293.3(GPR20):c.1039G>A(p.Ala347Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,608,014 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 0.000013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

GPR20
NM_005293.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0130

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.053512335).

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.1039G>A	p.Ala347Thr	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.1039G>A	p.Ala347Thr	missense	Exon 2 of 2	ENSP00000366970.3	Q99678
GPR20	ENST00000887272.1		c.1039G>A	p.Ala347Thr	missense	Exon 2 of 2	ENSP00000557331.1
GPR20	ENST00000887273.1		c.1039G>A	p.Ala347Thr	missense	Exon 2 of 2	ENSP00000557332.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00000807

AC:

AN:

247778

AF XY:

0.0000149

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000893

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1455748

Hom.:

Cov.:

AF XY:

0.00000829

AC XY:

AN XY:

723410

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33400

American (AMR)

AF:

0.00

AC:

AN:

44566

Ashkenazi Jewish (ASJ)

AF:

0.0000384

AC:

AN:

26016

East Asian (EAS)

AF:

0.000152

AC:

AN:

39580

South Asian (SAS)

AF:

0.0000233

AC:

AN:

85982

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.00000361

AC:

AN:

1108766

Other (OTH)

AF:

0.0000333

AC:

AN:

60134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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:

0.0000131

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41476

American (AMR)

AF:

0.0000654

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

0.067

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.69

CADD

Benign

6.7

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0058

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.43

M_CAP

Benign

0.013

MetaRNN

Benign

0.054

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

-0.013

PrimateAI

Benign

0.29

PROVEAN

Benign

0.60

REVEL

Benign

0.016

Sift

Benign

0.28

Sift4G

Benign

0.57

Polyphen

0.0020

Vest4

0.052

MVP

0.39

MPC

0.27

ClinPred

0.050

GERP RS

0.29

Varity_R

0.028

gMVP

0.36

Mutation Taster

=97/3

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over