NM_020752.3:c.119C>A

Variant names:

• chr10-25175539-C-A
• NM_020752.3:c.119C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020752.3(GPR158):​c.119C>A​(p.Pro40Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 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)
• Consequence: GPR158 NM_020752.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0400
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053761244).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020752.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR158	NM_020752.3	MANE Select	c.119C>A	p.Pro40Gln	missense	Exon 1 of 11	NP_065803.2	Q5T848
	GPR158-AS1	NR_027333.2		n.601+137G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR158	ENST00000376351.4	TSL:1 MANE Select	c.119C>A	p.Pro40Gln	missense	Exon 1 of 11	ENSP00000365529.3	Q5T848
	GPR158	ENST00000650135.1		c.-119C>A		5_prime_UTR	Exon 2 of 12	ENSP00000498176.1	A0A3B3IUC3
	GPR158-AS1	ENST00000808924.1		n.786G>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	7.6
DANN	Benign	0.97
DEOGEN2	Benign	0.0088	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.0099	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.040
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.073
Sift	Benign	0.12	T
Sift4G	Benign	0.23	T
Polyphen		0.0020	B
Vest4		0.28
MutPred		0.16		Loss of glycosylation at P40 (P = 0.0145)
MVP		0.10
MPC		0.97
ClinPred		0.089	T
GERP RS		0.16
Varity_R		0.055
gMVP		0.24
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

hg19: chr10-25464468;