chr14-105051233-C-T

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

6
13

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]

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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
GPR132NM_013345.4 linkc.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
GPR132ENST00000329797.8 linkc.904G>A p.Val302Met missense_variant Exon 4 of 4 1 NM_013345.4 ENSP00000328818.3 Q9UNW8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251246
Hom.:
0
AF XY:
0.0000147
AC XY:
2
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:
16
AN:
1461294
Hom.:
0
Cov.:
32
AF XY:
0.0000124
AC XY:
9
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.:
32
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1

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
T
BayesDel_noAF
Benign
-0.32
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.71
D;.;D
Eigen
Benign
0.16
Eigen_PC
Benign
0.078
FATHMM_MKL
Benign
0.42
N
LIST_S2
Benign
0.83
.;T;T
M_CAP
Benign
0.056
D
MetaRNN
Benign
0.27
T;T;T
MetaSVM
Benign
-0.73
T
MutationAssessor
Uncertain
2.8
M;.;M
PrimateAI
Benign
0.44
T
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
D
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.

Other links and lift over

dbSNP: rs757180457; hg19: chr14-105517570; COSMIC: COSV100317562; COSMIC: COSV100317562; API