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GeneBe

10-25175832-G-A

Variant summary

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

The NM_020752.3(GPR158):c.412G>A(p.Val138Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,996 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: 0.0000014 ( 0 hom. )

Consequence

GPR158
NM_020752.3 missense

Scores

13

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.76
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-AS1 (HGNC:44163): (GPR158 antisense RNA 1)

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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=0.03847629).
BP6
Variant 10-25175832-G-A is Benign according to our data. Variant chr10-25175832-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3101568.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GPR158NM_020752.3 linkuse as main transcriptc.412G>A p.Val138Met missense_variant 1/11 ENST00000376351.4
GPR158-AS1NR_027333.2 linkuse as main transcriptn.445C>T non_coding_transcript_exon_variant 1/2
GPR158XR_930512.4 linkuse as main transcriptn.832G>A non_coding_transcript_exon_variant 1/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GPR158ENST00000376351.4 linkuse as main transcriptc.412G>A p.Val138Met missense_variant 1/111 NM_020752.3 P2
GPR158-AS1ENST00000449643.1 linkuse as main transcriptn.445C>T non_coding_transcript_exon_variant 1/22
GPR158ENST00000650135.1 linkuse as main transcriptc.175G>A p.Val59Met missense_variant 2/12 A2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460996
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726836
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

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 submitterclinical testingAmbry GeneticsNov 20, 2023This 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
0.071
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
Cadd
Benign
16
Dann
Benign
0.95
Eigen
Benign
-1.0
Eigen_PC
Benign
-0.72
FATHMM_MKL
Benign
0.019
N
LIST_S2
Benign
0.62
T;T
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.038
T;T
MetaSVM
Benign
-0.92
T
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.40
T
Polyphen
0.0010
.;B
Vest4
0.15
MutPred
0.27
.;Gain of catalytic residue at V138 (P = 0.0516);
MVP
0.043
MPC
0.81
ClinPred
0.28
T
GERP RS
2.3
Varity_R
0.024
gMVP
0.39

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.

Other links and lift over

dbSNP: rs1395305594; hg19: chr10-25464761; COSMIC: COSV66283435; API