Genetic Variant GPR132:p.Val302Met (chr14-105051233-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_013345.4(GPR132):c.904G>A(p.Val302Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

GPR132
NM_013345.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.378

Variant links:

Genes affected

GPR132 (HGNC:17482): (G protein-coupled receptor 132) This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor (GPCR) superfamily. The receptors are seven-pass transmembrane proteins that respond to extracellular cues and activate intracellular signal transduction pathways. This protein was reported to be a receptor for lysophosphatidylcholine action, but PubMedID: 15653487 retracts this finding and instead suggests this protein to be an effector of lysophosphatidylcholine action. This protein may have proton-sensing activity and may be a receptor for oxidized free fatty acids. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

GPR132 links:

LOC124903398 (HGNC:):

LOC124903398 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26952887).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR132	NM_013345.4 link	c.904G>A	p.Val302Met	missense_variant	Exon 4 of 4	ENST00000329797.8	NP_037477.1	Q9UNW8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR132	ENST00000329797.8 link	c.904G>A	p.Val302Met	missense_variant	Exon 4 of 4	1	NM_013345.4	ENSP00000328818.3		Q9UNW8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251246

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135828

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:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461294

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726802

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:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000990

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.904G>A (p.V302M) alteration is located in exon 4 (coding exon 2) of the GPR132 gene. This alteration results from a G to A substitution at nucleotide position 904, causing the valine (V) at amino acid position 302 to be replaced by a methionine (M). 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

0.17

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.71

D;.;D

Eigen

Benign

0.16

Eigen_PC

Benign

0.078

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.83

.;T;T

M_CAP

Benign

0.056

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.8

M;.;M

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.4

N;N;N

REVEL

Benign

0.19

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.015

D;D;D

Polyphen

0.98

D;.;D

Vest4

0.27

MutPred

0.67

Gain of catalytic residue at S297 (P = 0);.;Gain of catalytic residue at S297 (P = 0);

MVP

0.55

MPC

1.2

ClinPred

0.85

GERP RS

3.8

Varity_R

0.30

gMVP

0.41

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