X-79171491-T-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_032553.3(GPR174):​c.484T>C​(p.Ser162Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.52 (10886 hom., 16548 hem., cov: 22)
  • Exomes 𝑓: 0.58 (123676 hom. 209241 hem.)
  • Failed GnomAD Quality Control
• Consequence: GPR174 NM_032553.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.10
• Publications: 40 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.6999245E-4).
• BP6: Variant X-79171491-T-C is Benign according to our data. Variant chrX-79171491-T-C is described in ClinVar as [Benign]. Clinvar id is 3058904.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR174	NM_032553.3	c.484T>C	p.Ser162Pro	missense_variant	Exon 3 of 3	ENST00000645147.2	NP_115942.1
GPR174	XM_047442579.1	c.484T>C	p.Ser162Pro	missense_variant	Exon 3 of 3		XP_047298535.1
GPR174	XM_047442580.1	c.484T>C	p.Ser162Pro	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>C	p.Ser162Pro	missense_variant	Exon 3 of 3		NM_032553.3	ENSP00000494310.1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 56891 AN: 109918 Hom.: 10891 Cov.: 22

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.514

GnomAD2 exomes AF: 0.513 AC: 93710 AN: 182645 AF XY: 0.534

Gnomad AFR exome AF: 0.413

Gnomad AMR exome AF: 0.272

Gnomad ASJ exome AF: 0.487

Gnomad EAS exome AF: 0.398

Gnomad FIN exome AF: 0.629

Gnomad NFE exome AF: 0.603

Gnomad OTH exome AF: 0.557

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.575 AC: 631340 AN: 1097943 Hom.: 123676 Cov.: 47 AF XY: 0.576 AC XY: 209241 AN XY: 363347

African (AFR) AF: 0.417 AC: 10996 AN: 26393

American (AMR) AF: 0.286 AC: 10058 AN: 35185

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 9396 AN: 19380

East Asian (EAS) AF: 0.472 AC: 14257 AN: 30197

South Asian (SAS) AF: 0.521 AC: 28203 AN: 54140

European-Finnish (FIN) AF: 0.629 AC: 25462 AN: 40509

Middle Eastern (MID) AF: 0.604 AC: 2500 AN: 4136

European-Non Finnish (NFE) AF: 0.599 AC: 504666 AN: 841925

Other (OTH) AF: 0.560 AC: 25802 AN: 46078

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.517 AC: 56905 AN: 109971 Hom.: 10886 Cov.: 22 AF XY: 0.513 AC XY: 16548 AN XY: 32273

African (AFR) AF: 0.413 AC: 12536 AN: 30318

American (AMR) AF: 0.418 AC: 4324 AN: 10347

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1248 AN: 2630

East Asian (EAS) AF: 0.397 AC: 1365 AN: 3441

South Asian (SAS) AF: 0.516 AC: 1317 AN: 2552

European-Finnish (FIN) AF: 0.635 AC: 3619 AN: 5701

Middle Eastern (MID) AF: 0.531 AC: 112 AN: 211

European-Non Finnish (NFE) AF: 0.593 AC: 31210 AN: 52594

Other (OTH) AF: 0.516 AC: 776 AN: 1505

Alfa AF: 0.552 Hom.: 82737

Bravo AF: 0.494

TwinsUK AF: 0.584 AC: 2166

ALSPAC AF: 0.580 AC: 1676

ESP6500AA AF: 0.420 AC: 1610

ESP6500EA AF: 0.595 AC: 4000

ExAC AF: 0.528 AC: 64093

EpiCase AF: 0.589

EpiControl AF: 0.602

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

GPR174-related disorder Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.31
DANN	Benign	0.80
DEOGEN2	Benign	0.019	T;T
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Benign	0.13	.;T
MetaRNN	Benign	0.00017	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.59	N;N
PhyloP100		-2.1
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.3	.;N
REVEL	Benign	0.10
Sift	Benign	0.32	.;T
Sift4G	Benign	0.32	.;T
Polyphen		0.0	B;B
Vest4		0.012
MPC		0.32
ClinPred		0.0088	T
GERP RS		-0.73
Varity_R		0.14
gMVP		0.63
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3827440; hg19: chrX-78426988; COSMIC: COSV52133812;