rs1569282719

Variant names:

• chrX-79171470-C-T
• rs1569282719
• NM_032553.3:c.463C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.19
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.463C>T	p.Leu155Phe	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.463C>T	p.Leu155Phe	missense	Exon 3 of 3	ENSP00000494310.1	Q9BXC1
	GPR174	ENST00000871945.1		c.463C>T	p.Leu155Phe	missense	Exon 2 of 2	ENSP00000542004.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD2 exomes AF: 0.00000547 AC: 1 AN: 182871 AF XY: 0.00

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 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

African (AFR) AF: 0.00 AC: 0 AN: 26393

American (AMR) AF: 0.00 AC: 0 AN: 35202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19368

East Asian (EAS) AF: 0.00 AC: 0 AN: 30199

South Asian (SAS) AF: 0.00 AC: 0 AN: 54132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4130

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841881

Other (OTH) AF: 0.0000217 AC: 1 AN: 46088

GnomAD4 genome Cov.: 22

Alfa AF: 0.000111 Hom.: 0

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.2
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
Vest4		0.14
MutPred		0.58		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
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs1569282719; hg19: chrX-78426967;