10-25412412-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020752.3(GPR158):c.1274C>G(p.Ala425Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 1,612,848 control chromosomes in the GnomAD database, including 389,197 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.60 (29420 hom., cov: 33)
  • Exomes 𝑓: 0.69 (359777 hom.)
• Consequence: GPR158 NM_020752.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.28

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.6245707E-6).
• BP6: Variant 10-25412412-C-G is Benign according to our data. Variant chr10-25412412-C-G is described in ClinVar as [Benign]. Clinvar id is 1294578.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR158	NM_020752.3	c.1274C>G	p.Ala425Gly	missense_variant	4/11	ENST00000376351.4
GPR158	XR_930512.4	n.1694C>G		non_coding_transcript_exon_variant	4/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR158	ENST00000376351.4	c.1274C>G	p.Ala425Gly	missense_variant	4/11	1	NM_020752.3	P2
GPR158	ENST00000650135.1	c.1037C>G	p.Ala346Gly	missense_variant	5/12			A2

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91930 AN: 151926 Hom.: 29412 Cov.: 33

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.620

GnomAD3 exomes AF: 0.611 AC: 153512 AN: 251442 Hom.: 50543 AF XY: 0.627 AC XY: 85163 AN XY: 135890

Gnomad AFR exome AF: 0.459

Gnomad AMR exome AF: 0.459

Gnomad ASJ exome AF: 0.687

Gnomad EAS exome AF: 0.148

Gnomad SAS exome AF: 0.663

Gnomad FIN exome AF: 0.600

Gnomad NFE exome AF: 0.732

Gnomad OTH exome AF: 0.642

GnomAD4 exome AF: 0.692 AC: 1010467 AN: 1460804 Hom.: 359777 Cov.: 43 AF XY: 0.693 AC XY: 503742 AN XY: 726776

Gnomad4 AFR exome AF: 0.456

Gnomad4 AMR exome AF: 0.469

Gnomad4 ASJ exome AF: 0.685

Gnomad4 EAS exome AF: 0.130

Gnomad4 SAS exome AF: 0.667

Gnomad4 FIN exome AF: 0.607

Gnomad4 NFE exome AF: 0.736

Gnomad4 OTH exome AF: 0.659

GnomAD4 genome AF: 0.605 AC: 91971 AN: 152044 Hom.: 29420 Cov.: 33 AF XY: 0.593 AC XY: 44027 AN XY: 74294

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.681

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.647

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.728

Gnomad4 OTH AF: 0.622

Alfa AF: 0.688 Hom.: 25850

Bravo AF: 0.589

TwinsUK AF: 0.746 AC: 2766

ALSPAC AF: 0.716 AC: 2758

ESP6500AA AF: 0.479 AC: 2112

ESP6500EA AF: 0.728 AC: 6264

ExAC AF: 0.623 AC: 75626

Asia WGS AF: 0.415 AC: 1446 AN: 3478

EpiCase AF: 0.728

EpiControl AF: 0.722

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	16
Dann	Uncertain	0.99
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.0096
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.84	T;T
MetaRNN	Benign	0.0000016	T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	0.94	P
PrimateAI	Benign	0.47	T
Polyphen		0.0040	.;B
Vest4		0.064
MPC		0.097
ClinPred		0.011	T
GERP RS		4.0
Varity_R		0.20
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2480345; hg19: chr10-25701341; COSMIC: COSV66266532;