8-141356978-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005293.3(GPR20):​c.946G>A​(p.Gly316Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,613,056 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 (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

GPR20
NM_005293.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.16
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.009430975).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPR20NM_005293.3 linkc.946G>A p.Gly316Arg 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
GPR20ENST00000377741.4 linkc.946G>A p.Gly316Arg missense_variant Exon 2 of 2 3 NM_005293.3 ENSP00000366970.3 Q99678

Frequencies

GnomAD3 genomes
AF:
0.000230
AC:
35
AN:
152276
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000265
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00105
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000252
AC:
63
AN:
250034
Hom.:
0
AF XY:
0.000192
AC XY:
26
AN XY:
135544
show subpopulations
Gnomad AFR exome
AF:
0.000494
Gnomad AMR exome
AF:
0.00119
Gnomad ASJ exome
AF:
0.000199
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000711
Gnomad OTH exome
AF:
0.000654
GnomAD4 exome
AF:
0.000112
AC:
164
AN:
1460780
Hom.:
0
Cov.:
30
AF XY:
0.0000908
AC XY:
66
AN XY:
726716
show subpopulations
Gnomad4 AFR exome
AF:
0.000388
Gnomad4 AMR exome
AF:
0.00123
Gnomad4 ASJ exome
AF:
0.0000765
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000666
Gnomad4 OTH exome
AF:
0.000215
GnomAD4 genome
AF:
0.000230
AC:
35
AN:
152276
Hom.:
0
Cov.:
33
AF XY:
0.000255
AC XY:
19
AN XY:
74398
show subpopulations
Gnomad4 AFR
AF:
0.000265
Gnomad4 AMR
AF:
0.00105
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00143
Alfa
AF:
0.0000970
Hom.:
0
Bravo
AF:
0.000385
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000264
AC:
32
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 01, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.946G>A (p.G316R) alteration is located in exon 2 (coding exon 1) of the GPR20 gene. This alteration results from a G to A substitution at nucleotide position 946, causing the glycine (G) at amino acid position 316 to be replaced by an arginine (R). 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
0.065
BayesDel_addAF
Benign
-0.57
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
9.2
DANN
Benign
0.79
DEOGEN2
Benign
0.0040
T
Eigen
Benign
-0.96
Eigen_PC
Benign
-0.99
FATHMM_MKL
Benign
0.20
N
LIST_S2
Benign
0.44
T
M_CAP
Benign
0.0019
T
MetaRNN
Benign
0.0094
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L
PrimateAI
Benign
0.30
T
PROVEAN
Benign
0.22
N
REVEL
Benign
0.0080
Sift
Benign
0.55
T
Sift4G
Benign
0.47
T
Polyphen
0.22
B
Vest4
0.12
MutPred
0.24
Gain of solvent accessibility (P = 0.0456);
MVP
0.30
MPC
0.34
ClinPred
0.0034
T
GERP RS
2.3
Varity_R
0.039
gMVP
0.17

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.

Other links and lift over

dbSNP: rs201855453; hg19: chr8-142367078; COSMIC: COSV100897441; COSMIC: COSV100897441; API