Variant X-79171396-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_032553.3(GPR174):c.389A>G(p.Lys130Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000546 in 1,098,211 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000055 ( 0 hom. 3 hem. )

Consequence

GPR174
NM_032553.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.79

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 -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR174	NM_032553.3 linkuse as main transcript	c.389A>G	p.Lys130Arg	missense_variant	3/3	ENST00000645147.2	NP_115942.1	Q9BXC1
GPR174	XM_047442579.1 linkuse as main transcript	c.389A>G	p.Lys130Arg	missense_variant	3/3		XP_047298535.1
GPR174	XM_047442580.1 linkuse as main transcript	c.389A>G	p.Lys130Arg	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.389A>G	p.Lys130Arg	missense_variant	3/3		NM_032553.3	ENSP00000494310.1		Q9BXC1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000546

AC:

AN:

1098211

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

363579

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:

0.00000712

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 17, 2024

The c.389A>G (p.K130R) alteration is located in exon 1 (coding exon 1) of the GPR174 gene. This alteration results from a A to G substitution at nucleotide position 389, causing the lysine (K) at amino acid position 130 to be replaced by an arginine (R). 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

0.082

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

T;T

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.59

.;T

M_CAP

Benign

0.0081

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.67

N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.58

.;N

REVEL

Benign

0.12

Sift

Benign

0.40

.;T

Sift4G

Benign

0.45

.;T

Polyphen

0.24

B;B

Vest4

0.12

MutPred

0.53

Loss of ubiquitination at K130 (P = 0.0412);Loss of ubiquitination at K130 (P = 0.0412);

MVP

0.20

MPC

0.27

ClinPred

0.77

GERP RS

5.1

Varity_R

0.17

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.21

Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over