rs10828833

Positions:

• chr10-25599251-A-C
• chr10-25599251-A-G

Variant summary

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

The NM_020752.3(GPR158):​c.3625A>C​(p.Ile1209Leu) 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 1,459,000 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I1209V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GPR158 NM_020752.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.874

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]

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=0.05867046).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR158	NM_020752.3	c.3625A>C	p.Ile1209Leu	missense_variant	11/11	ENST00000376351.4
GPR158	XM_017016452.3	c.2065A>C	p.Ile689Leu	missense_variant	8/8
GPR158	XR_930512.4	n.4045A>C		non_coding_transcript_exon_variant	11/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR158	ENST00000376351.4	c.3625A>C	p.Ile1209Leu	missense_variant	11/11	1	NM_020752.3	P2
GPR158	ENST00000490549.1	n.1812A>C		non_coding_transcript_exon_variant	3/3	1
GPR158	ENST00000650135.1	c.3388A>C	p.Ile1130Leu	missense_variant	12/12			A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1459000 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 725966

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.00

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.8
DANN	Benign	0.88
DEOGEN2	Benign	0.0079	.;T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.66
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.17	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.059	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	.;N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.17	.;N
REVEL	Benign	0.078
Sift	Benign	0.058	.;T
Sift4G	Benign	0.15	.;T
Polyphen		0.0020	.;B
Vest4		0.12
MutPred		0.14		.;Loss of ubiquitination at K1214 (P = 0.0801);
MVP		0.17
MPC		0.094
ClinPred		0.038	T
GERP RS		3.1
Varity_R		0.057
gMVP		0.052

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

LitVar

Other links and lift over

dbSNP: rs10828833; hg19: chr10-25888180;