Variant 15-39801247-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007223.3(GPR176):c.1433C>A(p.Pro478His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

GPR176
NM_007223.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0

Variant links:

Genes affected

GPR176 (HGNC:32370): (G protein-coupled receptor 176) Members of the G protein-coupled receptor family, such as GPR176, are cell surface receptors involved in responses to hormones, growth factors, and neurotransmitters (Hata et al., 1995 [PubMed 7893747]).[supplied by OMIM, Jul 2008]

GPR176 links:

ENSG00000259580 (HGNC:):

ENSG00000259580 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR176	NM_007223.3 linkuse as main transcript	c.1433C>A	p.Pro478His	missense_variant	3/3	ENST00000561100.2	NP_009154.1	Q14439-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GPR176	ENST00000561100.2 linkuse as main transcript	c.1433C>A	p.Pro478His	missense_variant	3/3	1	NM_007223.3	ENSP00000453076.1	Q14439-1
GPR176	ENST00000299092.4 linkuse as main transcript	c.1430C>A	p.Pro477His	missense_variant	4/4	1		ENSP00000299092.3	Q14439-3
GPR176	ENST00000543580.7 linkuse as main transcript	c.1298C>A	p.Pro433His	missense_variant	3/3	2		ENSP00000439361.1	Q14439-2
ENSG00000259580	ENST00000558616.1 linkuse as main transcript	n.87C>A		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251450

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

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:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461840

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

8.99e-7

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

Nov 26, 2024

The c.1433C>A (p.P478H) alteration is located in exon 3 (coding exon 3) of the GPR176 gene. This alteration results from a C to A substitution at nucleotide position 1433, causing the proline (P) at amino acid position 478 to be replaced by a histidine (H). 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

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Pathogenic

0.20

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

.;T;.

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.94

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.060

MetaRNN

Uncertain

0.49

T;T;T

MetaSVM

Uncertain

0.55

MutationAssessor

Benign

2.0

.;M;.

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-2.2

N;N;N

REVEL

Uncertain

0.38

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.55

MutPred

0.23

.;Loss of catalytic residue at P477 (P = 0.0187);.;

MVP

0.99

MPC

1.3

ClinPred

0.82

GERP RS

6.2

Varity_R

0.50

gMVP

0.44

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

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