10-25175904-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_020752.3(GPR158):c.484T>C(p.Trp162Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,504 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 Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GPR158
NM_020752.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.397

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05309257).

BP6

Variant 10-25175904-T-C is Benign according to our data. Variant chr10-25175904-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2616115.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GPR158	NM_020752.3 linkuse as main transcript	c.484T>C	p.Trp162Arg	missense_variant	1/11	ENST00000376351.4
GPR158-AS1	NR_027333.2 linkuse as main transcript	n.373A>G		non_coding_transcript_exon_variant	1/2
GPR158	XR_930512.4 linkuse as main transcript	n.904T>C		non_coding_transcript_exon_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GPR158	ENST00000376351.4 linkuse as main transcript	c.484T>C	p.Trp162Arg	missense_variant	1/11	1	NM_020752.3	P2
GPR158-AS1	ENST00000449643.1 linkuse as main transcript	n.373A>G		non_coding_transcript_exon_variant	1/2	2
GPR158	ENST00000650135.1 linkuse as main transcript	c.247T>C	p.Trp83Arg	missense_variant	2/12			A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248670

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134678

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:

6.84e-7

AC:

AN:

1461504

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727070

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.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

Cadd

Benign

Dann

Benign

0.66

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.13

T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.053

T;T

MetaSVM

Benign

-0.94

MutationTaster

Benign

1.0

PrimateAI

Benign

0.48

Polyphen

0.0

.;B

Vest4

0.28

MutPred

0.51

.;Loss of catalytic residue at L160 (P = 0.0018);

MVP

0.043

MPC

1.4

ClinPred

0.067

GERP RS

3.9

Varity_R

0.078

gMVP

0.68

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