Genetic Variant GPR158:p.Trp112Gly (chr10-25175754-T-G) – 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.334T>G(p.Trp112Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GPR158
NM_020752.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.20

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=0.051354498).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR158	NM_020752.3 link	c.334T>G	p.Trp112Gly	missense_variant	Exon 1 of 11	ENST00000376351.4	NP_065803.2	Q5T848
GPR158-AS1	NR_027333.2 link	n.523A>C		non_coding_transcript_exon_variant	Exon 1 of 2
GPR158	XR_930512.4 link	n.754T>G		non_coding_transcript_exon_variant	Exon 1 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GPR158	ENST00000376351.4 link	c.334T>G	p.Trp112Gly	missense_variant	Exon 1 of 11	1	NM_020752.3	ENSP00000365529.3	Q5T848
GPR158	ENST00000650135.1 link	c.97T>G	p.Trp33Gly	missense_variant	Exon 2 of 12			ENSP00000498176.1	A0A3B3IUC3
GPR158-AS1	ENST00000449643.1 link	n.523A>C		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458650

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725816

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.334T>G (p.W112G) alteration is located in exon 1 (coding exon 1) of the GPR158 gene. This alteration results from a T to G substitution at nucleotide position 334, causing the tryptophan (W) at amino acid position 112 to be replaced by a glycine (G). 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

0.042

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.68

DEOGEN2

Benign

0.0057

.;T

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.22

T;T

M_CAP

Benign

0.033

MetaRNN

Benign

0.051

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;N

PrimateAI

Benign

0.40

PROVEAN

Benign

1.0

.;N

REVEL

Benign

0.036

Sift

Benign

0.56

.;T

Sift4G

Benign

0.55

.;T

Polyphen

0.0

.;B

Vest4

0.32

MutPred

0.38

.;Gain of disorder (P = 0.0012);

MVP

0.043

MPC

1.4

ClinPred

0.041

GERP RS

0.72

Varity_R

0.060

gMVP

0.58

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over