Genetic Variant GPR174:p.Thr161Thr (chrX-79171490-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

1 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: Benign. The variant received -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 VariationId 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. GnomAdExome4 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 GnomAdExome4. There are 159 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 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.483C>T	p.Thr161Thr	synonymous	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.483C>T	p.Thr161Thr	synonymous	Exon 3 of 3	ENSP00000494310.1	Q9BXC1
	GPR174	ENST00000871945.1		c.483C>T	p.Thr161Thr	synonymous	Exon 2 of 2	ENSP00000542004.1

Frequencies

GnomAD3 genomes

AF:

0.00456

AC:

507

AN:

111176

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00134

AC:

245

AN:

182921

AF XY:

0.000991

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 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

African (AFR)

AF:

0.0171

AC:

451

AN:

26394

American (AMR)

AF:

0.000625

AC:

AN:

35203

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19382

East Asian (EAS)

AF:

0.00

AC:

AN:

30199

South Asian (SAS)

AF:

0.000129

AC:

AN:

54140

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40515

Middle Eastern (MID)

AF:

0.000967

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.0000143

AC:

AN:

842005

Other (OTH)

AF:

0.00122

AC:

AN:

46087

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

114

143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00456

AC:

507

AN:

111231

Hom.:

Cov.:

AF XY:

0.00451

AC XY:

151

AN XY:

33445

show subpopulations

African (AFR)

AF:

0.0159

AC:

487

AN:

30637

American (AMR)

AF:

0.00134

AC:

AN:

10453

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2645

East Asian (EAS)

AF:

0.00

AC:

AN:

3533

South Asian (SAS)

AF:

0.00

AC:

AN:

2603

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5983

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

52956

Other (OTH)

AF:

0.00330

AC:

AN:

1517

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000300

Hom.:

Bravo

AF:

0.00550

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

GPR174-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.17

(source)

DANN

Benign

0.29

PhyloP100

-3.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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