X-79171491-T-G

Variant names:

• chrX-79171491-T-G
• rs3827440
• NM_032553.3:c.484T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032553.3(GPR174):​c.484T>G​(p.Ser162Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S162P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 22)
• Consequence: GPR174 NM_032553.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037806004).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR174	NM_032553.3	c.484T>G	p.Ser162Ala	missense_variant	Exon 3 of 3	ENST00000645147.2	NP_115942.1
GPR174	XM_047442579.1	c.484T>G	p.Ser162Ala	missense_variant	Exon 3 of 3		XP_047298535.1
GPR174	XM_047442580.1	c.484T>G	p.Ser162Ala	missense_variant	Exon 2 of 2		XP_047298536.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR174	ENST00000645147.2	c.484T>G	p.Ser162Ala	missense_variant	Exon 3 of 3		NM_032553.3	ENSP00000494310.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.092
DANN	Benign	0.43
DEOGEN2	Benign	0.016	T;T
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.091	.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.038	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.13	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.86	.;N
REVEL	Benign	0.069
Sift	Benign	0.82	.;T
Sift4G	Benign	0.79	.;T
Polyphen		0.0	B;B
Vest4		0.014
MutPred		0.42		Loss of disorder (P = 0.0349);Loss of disorder (P = 0.0349);
MVP		0.093
MPC		0.21
ClinPred		0.030	T
GERP RS		-0.73
Varity_R		0.066
gMVP		0.36

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

LitVar

Other links and lift over

dbSNP: rs3827440; hg19: chrX-78426988;