10-25599251-A-G

Variant names:

• chr10-25599251-A-G
• rs10828833
• NM_020752.3:c.3625A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020752.3(GPR158):​c.3625A>G​(p.Ile1209Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 1,609,174 control chromosomes in the GnomAD database, including 188,620 homozygotes. 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: 𝑓 0.58 (28959 hom., cov: 31)
  • Exomes 𝑓: 0.46 (159661 hom.)
• Consequence: GPR158 NM_020752.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.874
• Publications: 29 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.771142E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR158	NM_020752.3	MANE Select	c.3625A>G	p.Ile1209Val	missense	Exon 11 of 11	NP_065803.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR158	ENST00000376351.4	TSL:1 MANE Select	c.3625A>G	p.Ile1209Val	missense	Exon 11 of 11	ENSP00000365529.3
	GPR158	ENST00000490549.1	TSL:1	n.1812A>G		non_coding_transcript_exon	Exon 3 of 3
	GPR158	ENST00000650135.1		c.3388A>G	p.Ile1130Val	missense	Exon 12 of 12	ENSP00000498176.1

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88339 AN: 151930 Hom.: 28894 Cov.: 31

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.514

GnomAD2 exomes AF: 0.507 AC: 125842 AN: 248222 AF XY: 0.494

Gnomad AFR exome AF: 0.896

Gnomad AMR exome AF: 0.517

Gnomad ASJ exome AF: 0.383

Gnomad EAS exome AF: 0.769

Gnomad FIN exome AF: 0.491

Gnomad NFE exome AF: 0.424

Gnomad OTH exome AF: 0.461

GnomAD4 exome AF: 0.458 AC: 667390 AN: 1457126 Hom.: 159661 Cov.: 35 AF XY: 0.456 AC XY: 330927 AN XY: 725078

African (AFR) AF: 0.904 AC: 30229 AN: 33424

American (AMR) AF: 0.516 AC: 23072 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 9793 AN: 26076

East Asian (EAS) AF: 0.734 AC: 29137 AN: 39682

South Asian (SAS) AF: 0.497 AC: 42812 AN: 86152

European-Finnish (FIN) AF: 0.493 AC: 25500 AN: 51740

Middle Eastern (MID) AF: 0.341 AC: 1963 AN: 5752

European-Non Finnish (NFE) AF: 0.429 AC: 475699 AN: 1109358

Other (OTH) AF: 0.484 AC: 29185 AN: 60252

GnomAD4 genome AF: 0.582 AC: 88469 AN: 152048 Hom.: 28959 Cov.: 31 AF XY: 0.584 AC XY: 43403 AN XY: 74308

African (AFR) AF: 0.889 AC: 36886 AN: 41504

American (AMR) AF: 0.525 AC: 8021 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1359 AN: 3470

East Asian (EAS) AF: 0.753 AC: 3884 AN: 5158

South Asian (SAS) AF: 0.518 AC: 2489 AN: 4806

European-Finnish (FIN) AF: 0.488 AC: 5162 AN: 10572

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29323 AN: 67948

Other (OTH) AF: 0.515 AC: 1089 AN: 2114

Alfa AF: 0.473 Hom.: 59829

Bravo AF: 0.598

TwinsUK AF: 0.424 AC: 1573

ALSPAC AF: 0.421 AC: 1622

ESP6500AA AF: 0.867 AC: 3819

ESP6500EA AF: 0.424 AC: 3647

ExAC AF: 0.514 AC: 62359

Asia WGS AF: 0.648 AC: 2248 AN: 3478

EpiCase AF: 0.404

EpiControl AF: 0.398

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.4
DANN	Benign	0.16
DEOGEN2	Benign	0.0077	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	7.8e-7	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.87
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.42	N
REVEL	Benign	0.15
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.0060
MPC		0.079
ClinPred		0.0026	T
GERP RS		3.1
Varity_R		0.027
gMVP		0.053
Mutation Taster		=99/1	polymorphism (auto)

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: rs10828833; hg19: chr10-25888180; COSMIC: COSV66286195;