X-79171470-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032553.3(GPR174):​c.463C>T​(p.Leu155Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,911 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)
Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

GPR174
NM_032553.3 missense

Scores

2
5
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.19
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPR174NM_032553.3 linkc.463C>T p.Leu155Phe missense_variant Exon 3 of 3 ENST00000645147.2 NP_115942.1 Q9BXC1
GPR174XM_047442579.1 linkc.463C>T p.Leu155Phe missense_variant Exon 3 of 3 XP_047298535.1
GPR174XM_047442580.1 linkc.463C>T p.Leu155Phe missense_variant Exon 2 of 2 XP_047298536.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GPR174ENST00000645147.2 linkc.463C>T p.Leu155Phe missense_variant Exon 3 of 3 NM_032553.3 ENSP00000494310.1 Q9BXC1

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD3 exomes
AF:
0.00000547
AC:
1
AN:
182871
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
67533
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000222
GnomAD4 exome
AF:
9.11e-7
AC:
1
AN:
1097911
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
363299
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
Cov.:
22
Alfa
AF:
0.000111
Hom.:
0
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 18, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.463C>T (p.L155F) alteration is located in exon 1 (coding exon 1) of the GPR174 gene. This alteration results from a C to T substitution at nucleotide position 463, causing the leucine (L) at amino acid position 155 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Benign
-0.0043
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
21
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.030
T;T
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.57
.;T
M_CAP
Benign
0.030
D
MetaRNN
Uncertain
0.55
D;D
MetaSVM
Benign
-0.56
T
MutationAssessor
Benign
1.1
L;L
PrimateAI
Uncertain
0.48
T
PROVEAN
Benign
-1.9
.;N
REVEL
Uncertain
0.45
Sift
Uncertain
0.0070
.;D
Sift4G
Uncertain
0.011
.;D
Polyphen
1.0
D;D
Vest4
0.14
MutPred
0.58
Gain of loop (P = 0.0435);Gain of loop (P = 0.0435);
MVP
0.48
MPC
0.40
ClinPred
0.82
D
GERP RS
4.9
Varity_R
0.63
gMVP
0.57

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.

Other links and lift over

dbSNP: rs1569282719; hg19: chrX-78426967; API