Genetic Variant GPR142:p.Arg112Trp (chr17-74369558-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_181790.1(GPR142):c.334C>T(p.Arg112Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000303 in 1,553,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

GPR142
NM_181790.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.103

Variant links:

Genes affected

GPR142 (HGNC:20088): (G protein-coupled receptor 142) GPR142 is a member of the rhodopsin family of G protein-coupled receptors (GPRs) (Fredriksson et al., 2003 [PubMed 14623098]).[supplied by OMIM, Mar 2008]

GPR142 links:

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=0.02385649).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR142	NM_001331076.1 link	c.18C>T	p.Cys6Cys	synonymous_variant	Exon 2 of 4	ENST00000582579.6	NP_001318005.1	Q7Z601J3QSD0
GPR142	NM_181790.1 link	c.334C>T	p.Arg112Trp	missense_variant	Exon 2 of 4		NP_861455.1	Q7Z601
GPR142	NM_001331077.1 link	c.18C>T	p.Cys6Cys	synonymous_variant	Exon 2 of 4		NP_001318006.1	Q7Z601J3QSD0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GPR142	ENST00000335666.4 link	c.334C>T	p.Arg112Trp	missense_variant	Exon 2 of 4	1		ENSP00000335158.4	Q7Z601
GPR142	ENST00000582579.6 link	c.18C>T	p.Cys6Cys	synonymous_variant	Exon 2 of 4	1	NM_001331076.1	ENSP00000464632.2	J3QSD0
GPR142	ENST00000585308.6 link	c.18C>T	p.Cys6Cys	synonymous_variant	Exon 2 of 4	3		ENSP00000463521.2	J3QLF2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152032

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000685

AC:

AN:

160578

Hom.:

AF XY:

0.0000710

AC XY:

AN XY:

84506

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000867

Gnomad SAS exome

AF:

0.0000437

Gnomad FIN exome

AF:

0.0000595

Gnomad NFE exome

AF:

0.0000799

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000321

AC:

AN:

1401388

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

691398

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000836

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000278

Gnomad4 SAS exome

AF:

0.0000378

Gnomad4 FIN exome

AF:

0.0000202

Gnomad4 NFE exome

AF:

0.0000296

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152032

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74244

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000115

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000282

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 28, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.334C>T (p.R112W) alteration is located in exon 2 (coding exon 2) of the GPR142 gene. This alteration results from a C to T substitution at nucleotide position 334, causing the arginine (R) at amino acid position 112 to be replaced by a tryptophan (W). 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

0.090

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0038

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0074

LIST_S2

Benign

0.58

M_CAP

Benign

0.042

MetaRNN

Benign

0.024

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.4

REVEL

Benign

0.13

Sift

Benign

0.067

Sift4G

Pathogenic

0.0

Polyphen

0.0020

Vest4

0.14

MVP

0.66

MPC

0.12

ClinPred

0.055

GERP RS

-1.8

Varity_R

0.037

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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