chr10-25176000-G-A

Position:

• chr10-25176000-G-A

Variant summary

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

The NM_020752.3(GPR158):​c.580G>A​(p.Ala194Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 9.56

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR158	NM_020752.3	c.580G>A	p.Ala194Thr	missense_variant	1/11	ENST00000376351.4	NP_065803.2
GPR158-AS1	NR_027333.2	n.277C>T		non_coding_transcript_exon_variant	1/2
GPR158	XR_930512.4	n.1000G>A		non_coding_transcript_exon_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR158	ENST00000376351.4	c.580G>A	p.Ala194Thr	missense_variant	1/11	1	NM_020752.3	ENSP00000365529.3
GPR158	ENST00000650135.1	c.343G>A	p.Ala115Thr	missense_variant	2/12			ENSP00000498176.1
GPR158-AS1	ENST00000449643.1	n.277C>T		non_coding_transcript_exon_variant	1/2	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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2024

The c.580G>A (p.A194T) 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 580, causing the alanine (A) at amino acid position 194 to be replaced by a threonine (T). 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	Uncertain	0.51
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.39	.;T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Uncertain	2.4	.;M
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.6	.;D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.0040	.;D
Sift4G	Pathogenic	0.0	.;D
Polyphen		1.0	.;D
Vest4		0.73
MutPred		0.33		.;Gain of catalytic residue at A194 (P = 0.0419);
MVP		0.69
MPC		1.9
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.46
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-25464929;