dbSNP rs566727690: GPR158:p.Gly50Asp (chr10-25175569-G-A) – 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_020752.3(GPR158):c.149G>A(p.Gly50Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000559 in 1,611,046 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G50A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

GPR158
NM_020752.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.323

Variant links:

Genes affected

GPR158 (HGNC:23689): (G protein-coupled receptor 158) Predicted to enable G protein-coupled receptor activity. Predicted to act upstream of or within G protein-coupled receptor signaling pathway and protein localization to plasma membrane. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

GPR158 links:

GPR158-AS1 (HGNC:44163): (GPR158 antisense RNA 1)

GPR158-AS1 links:

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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=0.019054115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR158	NM_020752.3 link	c.149G>A	p.Gly50Asp	missense_variant	Exon 1 of 11	ENST00000376351.4	NP_065803.2	Q5T848
GPR158	XR_930512.4 link	n.569G>A		non_coding_transcript_exon_variant	Exon 1 of 12
GPR158-AS1	NR_027333.2 link	n.601+107C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GPR158	ENST00000376351.4 link	c.149G>A	p.Gly50Asp	missense_variant	Exon 1 of 11	1	NM_020752.3	ENSP00000365529.3	Q5T848
GPR158	ENST00000650135 link	c.-89G>A		5_prime_UTR_variant	Exon 2 of 12			ENSP00000498176.1	A0A3B3IUC3
GPR158-AS1	ENST00000449643.1 link	n.601+107C>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152182

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:

0.000583

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000208

AC:

AN:

240828

Hom.:

AF XY:

0.00000757

AC XY:

AN XY:

132068

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000279

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1458744

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725770

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000584

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000248

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0070

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.0076

LIST_S2

Benign

0.28

M_CAP

Benign

0.041

MetaRNN

Benign

0.019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.64

REVEL

Benign

0.082

Sift

Benign

0.35

Sift4G

Benign

0.23

Polyphen

0.0090

Vest4

0.10

MutPred

0.087

Loss of MoRF binding (P = 0.0593);

MVP

0.068

MPC

1.0

ClinPred

0.020

GERP RS

3.8

Varity_R

0.078

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over