X-79171490-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_032553.3(GPR174):c.483C>T(p.Thr161Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000876 in 1,209,292 control chromosomes in the GnomAD database, including 5 homozygotes. There are 310 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 3 hom., 151 hem., cov: 22)

Exomes 𝑓: 0.00050 ( 2 hom. 159 hem. )

Consequence

GPR174
NM_032553.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.28

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant X-79171490-C-T is Benign according to our data. Variant chrX-79171490-C-T is described in ClinVar as [Benign]. Clinvar id is 708865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.28 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000503 (552/1098061) while in subpopulation AFR AF= 0.0171 (451/26394). AF 95% confidence interval is 0.0158. There are 2 homozygotes in gnomad4_exome. There are 159 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR174	NM_032553.3 link	c.483C>T	p.Thr161Thr	synonymous_variant	Exon 3 of 3	ENST00000645147.2	NP_115942.1	Q9BXC1
GPR174	XM_047442579.1 link	c.483C>T	p.Thr161Thr	synonymous_variant	Exon 3 of 3		XP_047298535.1
GPR174	XM_047442580.1 link	c.483C>T	p.Thr161Thr	synonymous_variant	Exon 2 of 2		XP_047298536.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR174	ENST00000645147.2 link	c.483C>T	p.Thr161Thr	synonymous_variant	Exon 3 of 3		NM_032553.3	ENSP00000494310.1		Q9BXC1

Frequencies

GnomAD3 genomes

AF:

0.00456

AC:

507

AN:

111176

Hom.:

Cov.:

AF XY:

0.00452

AC XY:

151

AN XY:

33380

show subpopulations

Gnomad AFR

AF:

0.0159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00134

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000189

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00134

AC:

245

AN:

182921

Hom.:

AF XY:

0.000991

AC XY:

AN XY:

67581

show subpopulations

Gnomad AFR exome

AF:

0.0172

Gnomad AMR exome

AF:

0.000474

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.000887

GnomAD4 exome

AF:

0.000503

AC:

552

AN:

1098061

Hom.:

Cov.:

AF XY:

0.000437

AC XY:

159

AN XY:

363443

show subpopulations

Gnomad4 AFR exome

AF:

0.0171

Gnomad4 AMR exome

AF:

0.000625

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000143

Gnomad4 OTH exome

AF:

0.00122

GnomAD4 genome

AF:

0.00456

AC:

507

AN:

111231

Hom.:

Cov.:

AF XY:

0.00451

AC XY:

151

AN XY:

33445

show subpopulations

Gnomad4 AFR

AF:

0.0159

Gnomad4 AMR

AF:

0.00134

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.00330

Alfa

AF:

0.000300

Hom.:

Bravo

AF:

0.00550

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 24, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

GPR174-related disorder

Benign:1

Mar 26, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.17

DANN

Benign

0.29

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