Variant X-79171270-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_032553.3(GPR174):c.263C>A(p.Pro88His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00284 in 1,209,893 control chromosomes in the GnomAD database, including 8 homozygotes. There are 1,133 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0019 ( 2 hom., 52 hem., cov: 23)

Exomes 𝑓: 0.0029 ( 6 hom. 1081 hem. )

Consequence

GPR174
NM_032553.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.12

Variant links:

Genes affected

GPR174 (HGNC:30245): (G protein-coupled receptor 174) This gene encodes a protein belonging to the G protein-coupled receptor superfamily. These proteins are characterized by the presence of seven alpha-helical transmembrane domains, and they activate or interact with various endogenous or exogenous ligands, including neurotransmitters, hormones, and odorant and taste substances. This family member is classified as an orphan receptor because the cognate ligand has not been identified. [provided by RefSeq, Sep 2011]

GPR174 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007401705).

BP6

Variant X-79171270-C-A is Benign according to our data. Variant chrX-79171270-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3041228.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR174	NM_032553.3 linkuse as main transcript	c.263C>A	p.Pro88His	missense_variant	3/3	ENST00000645147.2	NP_115942.1	Q9BXC1
GPR174	XM_047442579.1 linkuse as main transcript	c.263C>A	p.Pro88His	missense_variant	3/3		XP_047298535.1
GPR174	XM_047442580.1 linkuse as main transcript	c.263C>A	p.Pro88His	missense_variant	2/2		XP_047298536.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR174	ENST00000645147.2 linkuse as main transcript	c.263C>A	p.Pro88His	missense_variant	3/3		NM_032553.3	ENSP00000494310.1		Q9BXC1

Frequencies

GnomAD3 genomes

AF:

0.00185

AC:

208

AN:

112172

Hom.:

Cov.:

AF XY:

0.00151

AC XY:

AN XY:

34358

show subpopulations

Gnomad AFR

AF:

0.000453

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00160

Gnomad ASJ

AF:

0.000377

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00298

Gnomad FIN

AF:

0.000328

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00308

Gnomad OTH

AF:

0.00133

GnomAD3 exomes

AF:

0.00220

AC:

401

AN:

181889

Hom.:

AF XY:

0.00241

AC XY:

161

AN XY:

66811

show subpopulations

Gnomad AFR exome

AF:

0.000685

Gnomad AMR exome

AF:

0.00183

Gnomad ASJ exome

AF:

0.000538

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00416

Gnomad FIN exome

AF:

0.000315

Gnomad NFE exome

AF:

0.00294

Gnomad OTH exome

AF:

0.00357

GnomAD4 exome

AF:

0.00294

AC:

3231

AN:

1097666

Hom.:

Cov.:

AF XY:

0.00298

AC XY:

1081

AN XY:

363100

show subpopulations

Gnomad4 AFR exome

AF:

0.000455

Gnomad4 AMR exome

AF:

0.00179

Gnomad4 ASJ exome

AF:

0.000413

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.00431

Gnomad4 FIN exome

AF:

0.000543

Gnomad4 NFE exome

AF:

0.00325

Gnomad4 OTH exome

AF:

0.00282

GnomAD4 genome

AF:

0.00185

AC:

208

AN:

112227

Hom.:

Cov.:

AF XY:

0.00151

AC XY:

AN XY:

34423

show subpopulations

Gnomad4 AFR

AF:

0.000452

Gnomad4 AMR

AF:

0.00160

Gnomad4 ASJ

AF:

0.000377

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00299

Gnomad4 FIN

AF:

0.000328

Gnomad4 NFE

AF:

0.00308

Gnomad4 OTH

AF:

0.00131

Alfa

AF:

0.00276

Hom.:

107

Bravo

AF:

0.00218

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00312

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00223

AC:

ExAC

AF:

0.00231

AC:

281

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GPR174-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 11, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.0052

T;T

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.64

.;T

M_CAP

Benign

0.0090

MetaRNN

Benign

0.0074

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.29

N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

0.33

.;N

REVEL

Benign

0.082

Sift

Benign

0.14

.;T

Sift4G

Benign

0.14

.;T

Polyphen

0.0

B;B

Vest4

0.057

MVP

0.16

MPC

0.29

ClinPred

0.0022

GERP RS

3.0

Varity_R

0.20

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over