Variant 10-25175839-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020752.3(GPR158):c.419T>A(p.Leu140Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

GPR158
NM_020752.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.66

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:):

GPR158-AS1 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, 0.808

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR158	NM_020752.3 linkuse as main transcript	c.419T>A	p.Leu140Gln	missense_variant	1/11	ENST00000376351.4	NP_065803.2	Q5T848
GPR158-AS1	NR_027333.2 linkuse as main transcript	n.438A>T		non_coding_transcript_exon_variant	1/2
GPR158	XR_930512.4 linkuse as main transcript	n.839T>A		non_coding_transcript_exon_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GPR158	ENST00000376351.4 linkuse as main transcript	c.419T>A	p.Leu140Gln	missense_variant	1/11	1	NM_020752.3	ENSP00000365529.3	Q5T848
GPR158	ENST00000650135.1 linkuse as main transcript	c.182T>A	p.Leu61Gln	missense_variant	2/12			ENSP00000498176.1	A0A3B3IUC3
GPR158-AS1	ENST00000449643.1 linkuse as main transcript	n.438A>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248398

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134574

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000900

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461258

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726974

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 11, 2024

The c.419T>A (p.L140Q) alteration is located in exon 1 (coding exon 1) of the GPR158 gene. This alteration results from a T to A substitution at nucleotide position 419, causing the leucine (L) at amino acid position 140 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

0.30

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

.;T

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.84

T;T

M_CAP

Pathogenic

0.50

MetaRNN

Pathogenic

0.81

D;D

MetaSVM

Uncertain

0.41

MutationAssessor

Uncertain

2.2

.;M

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-5.0

.;D

REVEL

Pathogenic

0.76

Sift

Uncertain

0.0010

.;D

Sift4G

Uncertain

0.0030

.;D

Polyphen

1.0

.;D

Vest4

0.87

MutPred

0.38

.;Gain of disorder (P = 0.0148);

MVP

0.50

MPC

1.9

ClinPred

0.99

GERP RS

4.0

Varity_R

0.77

gMVP

0.82

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