chr10-25175788-A-G

Position:

• chr10-25175788-A-G

Variant summary

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

The NM_020752.3(GPR158):​c.368A>G​(p.His123Arg) 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. 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: 2.52

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=0.16576338).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR158	NM_020752.3	c.368A>G	p.His123Arg	missense_variant	1/11	ENST00000376351.4	NP_065803.2
GPR158-AS1	NR_027333.2	n.489T>C		non_coding_transcript_exon_variant	1/2
GPR158	XR_930512.4	n.788A>G		non_coding_transcript_exon_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR158	ENST00000376351.4	c.368A>G	p.His123Arg	missense_variant	1/11	1	NM_020752.3	ENSP00000365529	P2
GPR158-AS1	ENST00000449643.1	n.489T>C		non_coding_transcript_exon_variant	1/2	2
GPR158	ENST00000650135.1	c.131A>G	p.His44Arg	missense_variant	2/12			ENSP00000498176	A2

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 31, 2024

The c.368A>G (p.H123R) alteration is located in exon 1 (coding exon 1) of the GPR158 gene. This alteration results from a A to G substitution at nucleotide position 368, causing the histidine (H) at amino acid position 123 to be replaced by an arginine (R). 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	0.078
BayesDel_addAF	Benign	0.00095	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	19
DANN	Benign	0.79
DEOGEN2	Benign	0.0063	.;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.99	.;L
MutationTaster	Benign	0.94	D
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.68	.;N
REVEL	Benign	0.24
Sift	Benign	0.52	.;T
Sift4G	Benign	0.86	.;T
Polyphen		0.011	.;B
Vest4		0.54
MutPred		0.18		.;Gain of phosphorylation at S121 (P = 0.1002);
MVP		0.34
MPC		0.99
ClinPred		0.46	T
GERP RS		4.5
Varity_R		0.13
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-25464717;