10-25175772-G-C

Position:

• chr10-25175772-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020752.3(GPR158):​c.352G>C​(p.Ala118Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,892 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GPR158 NM_020752.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.475

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059743464).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR158	NM_020752.3	c.352G>C	p.Ala118Pro	missense_variant	1/11	ENST00000376351.4	NP_065803.2
GPR158-AS1	NR_027333.2	n.505C>G		non_coding_transcript_exon_variant	1/2
GPR158	XR_930512.4	n.772G>C		non_coding_transcript_exon_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR158	ENST00000376351.4	c.352G>C	p.Ala118Pro	missense_variant	1/11	1	NM_020752.3	ENSP00000365529.3
GPR158	ENST00000650135.1	c.115G>C	p.Ala39Pro	missense_variant	2/12			ENSP00000498176.1
GPR158-AS1	ENST00000449643.1	n.505C>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458892 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725916

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

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

Oct 29, 2024

The c.352G>C (p.A118P) alteration is located in exon 1 (coding exon 1) of the GPR158 gene. This alteration results from a G to C substitution at nucleotide position 352, causing the alanine (A) at amino acid position 118 to be replaced by a proline (P). 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	0.076
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	7.6
DANN	Benign	0.94
DEOGEN2	Benign	0.0069	.;T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.44	T;T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.060	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.90	.;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.36	.;N
REVEL	Benign	0.28
Sift	Benign	0.13	.;T
Sift4G	Benign	0.21	.;T
Polyphen		0.0	.;B
Vest4		0.35
MutPred		0.20		.;Gain of glycosylation at A118 (P = 0.0372);
MVP		0.22
MPC		1.0
ClinPred		0.040	T
GERP RS		0.89
Varity_R		0.084
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: chr10-25464701;