10-25175566-C-G

Variant names:

• chr10-25175566-C-G
• rs754629829
• NM_020752.3:c.146C>G

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.146C>G​(p.Pro49Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P49L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GPR158 NM_020752.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281
• Publications: 1 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=0.040580094).

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.146C>G	p.Pro49Arg	missense	Exon 1 of 11	NP_065803.2	Q5T848
	GPR158-AS1	NR_027333.2		n.601+110G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR158	ENST00000376351.4	TSL:1 MANE Select	c.146C>G	p.Pro49Arg	missense	Exon 1 of 11	ENSP00000365529.3	Q5T848
	GPR158	ENST00000650135.1		c.-92C>G		5_prime_UTR	Exon 2 of 12	ENSP00000498176.1	A0A3B3IUC3
	GPR158-AS1	ENST00000808924.1		n.759G>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000833 AC: 2 AN: 240190 AF XY: 0.0000152

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000935

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458668 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 725740

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111780

Other (OTH) AF: 0.00 AC: 0 AN: 60332

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	9.4
DANN	Benign	0.95
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.0060	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.28
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.17
Sift	Benign	0.050	D
Sift4G	Benign	0.54	T
Polyphen		0.0080	B
Vest4		0.13
MutPred		0.20		Gain of MoRF binding (P = 0.0035)
MVP		0.18
MPC		1.0
ClinPred		0.050	T
GERP RS		-0.56
Varity_R		0.10
gMVP		0.30
Mutation Taster		=98/2	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

dbSNP: rs754629829; hg19: chr10-25464495;