Genetic Variant GPR174:p.Thr25Ile (chrX-79171081-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_032553.3(GPR174):c.74C>T(p.Thr25Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,203,667 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.000010 ( 0 hom. 4 hem. )

Consequence

GPR174
NM_032553.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.86

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18245351).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032553.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR174	NM_032553.3	MANE Select	c.74C>T	p.Thr25Ile	missense	Exon 3 of 3	NP_115942.1	Q9BXC1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR174	ENST00000645147.2	MANE Select	c.74C>T	p.Thr25Ile	missense	Exon 3 of 3	ENSP00000494310.1	Q9BXC1
	GPR174	ENST00000871945.1		c.74C>T	p.Thr25Ile	missense	Exon 2 of 2	ENSP00000542004.1

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

112232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000972

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000388

AC:

AN:

180520

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000229

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000101

AC:

AN:

1091379

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

357063

show subpopulations

African (AFR)

AF:

0.000152

AC:

AN:

26276

American (AMR)

AF:

0.000171

AC:

AN:

35140

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19303

East Asian (EAS)

AF:

0.00

AC:

AN:

30079

South Asian (SAS)

AF:

0.00

AC:

AN:

53796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40448

Middle Eastern (MID)

AF:

0.000243

AC:

AN:

4112

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

836394

Other (OTH)

AF:

0.00

AC:

AN:

45831

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000267

AC:

AN:

112288

Hom.:

Cov.:

AF XY:

0.0000580

AC XY:

AN XY:

34458

show subpopulations

African (AFR)

AF:

0.0000970

AC:

AN:

30931

American (AMR)

AF:

0.00

AC:

AN:

10649

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3567

South Asian (SAS)

AF:

0.00

AC:

AN:

2714

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6131

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53209

Other (OTH)

AF:

0.00

AC:

AN:

1528

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000136

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.034

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.82

M_CAP

Benign

0.0049

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.1

PhyloP100

2.9

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-2.0

REVEL

Benign

0.13

Sift

Benign

0.084

Sift4G

Benign

0.58

Polyphen

0.48

Vest4

0.62

MVP

0.24

MPC

0.36

ClinPred

0.10

GERP RS

4.1

Varity_R

0.19

gMVP

0.69

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over