Genetic Variant GPR155:p.Arg657Gln (chr2-174446654-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_152529.7(GPR155):c.1970G>A(p.Arg657Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000675 in 1,613,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R657G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

GPR155
NM_152529.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.75

Variant links:

Genes affected

GPR155 (HGNC:22951): (G protein-coupled receptor 155) Involved in cognition. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

GPR155 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.809

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR155	NM_152529.7 link	c.1970G>A	p.Arg657Gln	missense_variant	Exon 12 of 16	ENST00000392552.7	NP_689742.4	Q7Z3F1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GPR155	ENST00000392552.7 link	c.1970G>A	p.Arg657Gln	missense_variant	Exon 12 of 16	1	NM_152529.7	ENSP00000376335.2	Q7Z3F1
GPR155	ENST00000295500.8 link	c.1970G>A	p.Arg657Gln	missense_variant	Exon 13 of 17	1		ENSP00000295500.4	Q7Z3F1
GPR155	ENST00000392551.6 link	c.1970G>A	p.Arg657Gln	missense_variant	Exon 13 of 17	1		ENSP00000376334.2	Q7Z3F1
GPR155	ENST00000614352.4 link	c.1886G>A	p.Arg629Gln	missense_variant	Exon 11 of 15	1		ENSP00000481104.1	A0A087WXK4

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000716

AC:

AN:

251418

Hom.:

AF XY:

0.0000662

AC XY:

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.000149

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000636

AC:

AN:

1461578

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000801

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000105

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000724

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:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000116

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0000741

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 30, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1970G>A (p.R657Q) alteration is located in exon 13 (coding exon 11) of the GPR155 gene. This alteration results from a G to A substitution at nucleotide position 1970, causing the arginine (R) at amino acid position 657 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

Benign

0.23

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.32

.;T;T;T

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.97

D;.;.;D

M_CAP

Benign

0.082

MetaRNN

Pathogenic

0.81

D;D;D;D

MetaSVM

Uncertain

-0.18

MutationAssessor

Uncertain

2.6

.;M;M;M

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.6

.;D;D;D

REVEL

Uncertain

0.54

Sift

Uncertain

0.0050

.;D;D;D

Sift4G

Uncertain

0.035

D;D;D;D

Polyphen

1.0

.;D;D;D

Vest4

0.96

MVP

0.77

MPC

0.74

ClinPred

0.89

GERP RS

5.5

Varity_R

0.49

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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