Genetic Variant GPR20:p.Asp324Tyr (chr8-141356954-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005293.3(GPR20):c.970G>T(p.Asp324Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,612,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. D324D) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

GPR20
NM_005293.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.90

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13540092).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR20	NM_005293.3 link	c.970G>T	p.Asp324Tyr	missense_variant	Exon 2 of 2	ENST00000377741.4	NP_005284.2	Q99678Q59GP3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR20	ENST00000377741.4 link	c.970G>T	p.Asp324Tyr	missense_variant	Exon 2 of 2	3	NM_005293.3	ENSP00000366970.3		Q99678

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152276

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249964

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135482

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000199

AC:

AN:

1460704

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

726690

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000151

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.970G>T (p.D324Y) alteration is located in exon 2 (coding exon 1) of the GPR20 gene. This alteration results from a G to T substitution at nucleotide position 970, causing the aspartic acid (D) at amino acid position 324 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.032

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.71

M_CAP

Benign

0.013

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.7

REVEL

Benign

0.070

Sift

Uncertain

0.014

Sift4G

Uncertain

0.011

Polyphen

0.50

Vest4

0.28

MutPred

0.29

Gain of phosphorylation at D324 (P = 0.0225);

MVP

0.34

MPC

0.53

ClinPred

0.096

GERP RS

0.96

Varity_R

0.085

gMVP

0.42

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

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