10-25175497-G-A

Variant names:

• chr10-25175497-G-A
• NM_020752.3:c.77G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020752.3(GPR158):​c.77G>A​(p.Arg26His) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GPR158 NM_020752.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.557

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10088584).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR158	NM_020752.3	c.77G>A	p.Arg26His	missense_variant	Exon 1 of 11	ENST00000376351.4	NP_065803.2
GPR158	XR_930512.4	n.497G>A		non_coding_transcript_exon_variant	Exon 1 of 12
GPR158-AS1	NR_027333.2	n.601+179C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR158	ENST00000376351.4	c.77G>A	p.Arg26His	missense_variant	Exon 1 of 11	1	NM_020752.3	ENSP00000365529.3
GPR158	ENST00000650135	c.-161G>A		5_prime_UTR_variant	Exon 2 of 12			ENSP00000498176.1
GPR158-AS1	ENST00000449643.1	n.601+179C>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.77G>A (p.R26H) alteration is located in exon 1 (coding exon 1) of the GPR158 gene. This alteration results from a G to A substitution at nucleotide position 77, causing the arginine (R) at amino acid position 26 to be replaced by a histidine (H). 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	0.17
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0060	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.17
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.050	T
Polyphen		0.91	P
Vest4		0.28
MutPred		0.17		Loss of methylation at R26 (P = 0.0438);
MVP		0.25
MPC		1.7
ClinPred		0.57	D
GERP RS		2.8
Varity_R		0.071
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr10-25464426;