Genetic Variant GPR31:p.Arg112Gln (chr6-167157497-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005299.3(GPR31):c.335G>A(p.Arg112Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000263 in 1,613,252 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. R112W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

GPR31
NM_005299.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.73

Variant links:

Genes affected

GPR31 (HGNC:4486): (G protein-coupled receptor 31) Enables G protein-coupled receptor activity and arachidonic acid binding activity. Involved in G protein-coupled receptor signaling pathway and response to acidic pH. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

GPR31 links:

ENSG00000291286 (HGNC:):

ENSG00000291286 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40410218).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR31	NM_005299.3 link	c.335G>A	p.Arg112Gln	missense_variant	Exon 1 of 1	ENST00000366834.2	NP_005290.2	O00270

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GPR31	ENST00000366834.2 link	c.335G>A	p.Arg112Gln	missense_variant	Exon 1 of 1	6	NM_005299.3	ENSP00000355799.2	O00270
ENSG00000291286	ENST00000486697.2 link	n.123-6904C>T		intron_variant	Intron 2 of 3	5
ENSG00000291286	ENST00000539001.6 link	n.369-6904C>T		intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.000506

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000366

AC:

AN:

248684

Hom.:

AF XY:

0.000356

AC XY:

AN XY:

134774

show subpopulations

Gnomad AFR exome

AF:

0.000250

Gnomad AMR exome

AF:

0.000814

Gnomad ASJ exome

AF:

0.00100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000474

Gnomad NFE exome

AF:

0.000392

Gnomad OTH exome

AF:

0.000661

GnomAD4 exome

AF:

0.000238

AC:

348

AN:

1461078

Hom.:

Cov.:

AF XY:

0.000237

AC XY:

172

AN XY:

726854

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000829

Gnomad4 ASJ exome

AF:

0.00142

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000376

Gnomad4 NFE exome

AF:

0.000203

Gnomad4 OTH exome

AF:

0.000596

GnomAD4 genome

AF:

0.000506

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.000458

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.000957

Alfa

AF:

0.000293

Hom.:

Bravo

AF:

0.000548

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000387

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000416

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 24, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.335G>A (p.R112Q) alteration is located in exon 1 (coding exon 1) of the GPR31 gene. This alteration results from a G to A substitution at nucleotide position 335, causing the arginine (R) at amino acid position 112 to be replaced by a glutamine (Q). 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

Pathogenic

0.58

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Uncertain

0.050

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

Eigen

Benign

-0.050

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.66

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.40

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

3.6

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.6

REVEL

Pathogenic

0.65

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.051

Polyphen

1.0

Vest4

0.39

MVP

0.93

MPC

0.55

ClinPred

0.79

GERP RS

2.7

Varity_R

0.76

gMVP

0.63

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