Variant X-79171636-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_032553.3(GPR174):c.629T>C(p.Leu210Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000911 in 1,098,080 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000091 ( 0 hom. 4 hem. )

Consequence

GPR174
NM_032553.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.84

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11651632).

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR174	NM_032553.3 linkuse as main transcript	c.629T>C	p.Leu210Ser	missense_variant	3/3	ENST00000645147.2	NP_115942.1	Q9BXC1
GPR174	XM_047442579.1 linkuse as main transcript	c.629T>C	p.Leu210Ser	missense_variant	3/3		XP_047298535.1
GPR174	XM_047442580.1 linkuse as main transcript	c.629T>C	p.Leu210Ser	missense_variant	2/2		XP_047298536.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR174	ENST00000645147.2 linkuse as main transcript	c.629T>C	p.Leu210Ser	missense_variant	3/3		NM_032553.3	ENSP00000494310.1		Q9BXC1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000165

AC:

AN:

182089

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

67095

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:

0.000668

GnomAD4 exome

AF:

0.00000911

AC:

AN:

1098080

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

363476

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000516

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

Cov.:

Alfa

AF:

0.000445

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2021

The c.629T>C (p.L210S) alteration is located in exon 1 (coding exon 1) of the GPR174 gene. This alteration results from a T to C substitution at nucleotide position 629, causing the leucine (L) at amino acid position 210 to be replaced by a serine (S). 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

0.14

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.0085

T;T

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.36

.;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.61

.;N

REVEL

Benign

0.080

Sift

Benign

0.81

.;T

Sift4G

Benign

0.68

.;T

Polyphen

0.091

B;B

Vest4

0.35

MutPred

0.64

Gain of disorder (P = 0.0119);Gain of disorder (P = 0.0119);

MVP

0.25

MPC

0.36

ClinPred

0.085

GERP RS

3.9

Varity_R

0.13

gMVP

0.76

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over