Variant X-79171491-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_032553.3(GPR174):c.484T>C(p.Ser162Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.52 ( 10886 hom., 16548 hem., cov: 22)

Exomes 𝑓: 0.58 ( 123676 hom. 209241 hem. )

Failed GnomAD Quality Control

Consequence

GPR174
NM_032553.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.10

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.6999245E-4).

BP6

Variant X-79171491-T-C is Benign according to our data. Variant chrX-79171491-T-C is described in ClinVar as [Benign]. Clinvar id is 3058904.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GPR174	NM_032553.3 linkuse as main transcript	c.484T>C	p.Ser162Pro	missense_variant	3/3	ENST00000645147.2
GPR174	XM_047442579.1 linkuse as main transcript	c.484T>C	p.Ser162Pro	missense_variant	3/3
GPR174	XM_047442580.1 linkuse as main transcript	c.484T>C	p.Ser162Pro	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR174	ENST00000645147.2 linkuse as main transcript	c.484T>C	p.Ser162Pro	missense_variant	3/3		NM_032553.3	P1

Frequencies

GnomAD3 genomes

AF:

0.518

AC:

56891

AN:

109918

Hom.:

10891

Cov.:

AF XY:

0.513

AC XY:

16527

AN XY:

32210

show subpopulations

Gnomad AFR

AF:

0.414

Gnomad AMI

AF:

0.592

Gnomad AMR

AF:

0.418

Gnomad ASJ

AF:

0.475

Gnomad EAS

AF:

0.396

Gnomad SAS

AF:

0.517

Gnomad FIN

AF:

0.635

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.593

Gnomad OTH

AF:

0.514

GnomAD3 exomes

AF:

0.513

AC:

93710

AN:

182645

Hom.:

15701

AF XY:

0.534

AC XY:

35963

AN XY:

67305

show subpopulations

Gnomad AFR exome

AF:

0.413

Gnomad AMR exome

AF:

0.272

Gnomad ASJ exome

AF:

0.487

Gnomad EAS exome

AF:

0.398

Gnomad SAS exome

AF:

0.532

Gnomad FIN exome

AF:

0.629

Gnomad NFE exome

AF:

0.603

Gnomad OTH exome

AF:

0.557

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.575

AC:

631340

AN:

1097943

Hom.:

123676

Cov.:

AF XY:

0.576

AC XY:

209241

AN XY:

363347

show subpopulations

Gnomad4 AFR exome

AF:

0.417

Gnomad4 AMR exome

AF:

0.286

Gnomad4 ASJ exome

AF:

0.485

Gnomad4 EAS exome

AF:

0.472

Gnomad4 SAS exome

AF:

0.521

Gnomad4 FIN exome

AF:

0.629

Gnomad4 NFE exome

AF:

0.599

Gnomad4 OTH exome

AF:

0.560

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.517

AC:

56905

AN:

109971

Hom.:

10886

Cov.:

AF XY:

0.513

AC XY:

16548

AN XY:

32273

show subpopulations

Gnomad4 AFR

AF:

0.413

Gnomad4 AMR

AF:

0.418

Gnomad4 ASJ

AF:

0.475

Gnomad4 EAS

AF:

0.397

Gnomad4 SAS

AF:

0.516

Gnomad4 FIN

AF:

0.635

Gnomad4 NFE

AF:

0.593

Gnomad4 OTH

AF:

0.516

Alfa

AF:

0.564

Hom.:

65630

Bravo

AF:

0.494

TwinsUK

AF:

0.584

AC:

2166

ALSPAC

AF:

0.580

AC:

1676

ESP6500AA

AF:

0.420

AC:

1610

ESP6500EA

AF:

0.595

AC:

4000

ExAC

AF:

0.528

AC:

64093

EpiCase

AF:

0.589

EpiControl

AF:

0.602

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GPR174-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as 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

0.093

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.31

DANN

Benign

0.80

DEOGEN2

Benign

0.019

T;T

FATHMM_MKL

Benign

0.0027

LIST_S2

Benign

0.13

.;T

MetaRNN

Benign

0.00017

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.59

N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.3

.;N

REVEL

Benign

0.10

Sift

Benign

0.32

.;T

Sift4G

Benign

0.32

.;T

Polyphen

0.0

B;B

Vest4

0.012

MPC

0.32

ClinPred

0.0088

GERP RS

-0.73

Varity_R

0.14

gMVP

0.63

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

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