NM_013345.4:c.766G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_013345.4(GPR132):​c.766G>C​(p.Ala256Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A256V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

GPR132
NM_013345.4 missense

Scores

5
7
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.03
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.86

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPR132NM_013345.4 linkc.766G>C p.Ala256Pro 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.766G>C p.Ala256Pro missense_variant Exon 4 of 4 1 NM_013345.4 ENSP00000328818.3 Q9UNW8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251424
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135900
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:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
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
Aug 27, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.766G>C (p.A256P) alteration is located in exon 4 (coding exon 2) of the GPR132 gene. This alteration results from a G to C substitution at nucleotide position 766, causing the alanine (A) at amino acid position 256 to be replaced by a proline (P). 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
0.85
BayesDel_addAF
Uncertain
0.070
D
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.84
D;.;D
Eigen
Benign
0.022
Eigen_PC
Benign
-0.17
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.73
.;T;T
M_CAP
Pathogenic
0.34
D
MetaRNN
Pathogenic
0.86
D;D;D
MetaSVM
Benign
-0.45
T
MutationAssessor
Pathogenic
3.2
M;.;M
PrimateAI
Uncertain
0.60
T
PROVEAN
Uncertain
-4.2
D;D;D
REVEL
Uncertain
0.42
Sift
Benign
0.033
D;D;D
Sift4G
Uncertain
0.0090
D;D;D
Polyphen
1.0
D;.;D
Vest4
0.71
MutPred
0.64
Gain of catalytic residue at V261 (P = 0);.;Gain of catalytic residue at V261 (P = 0);
MVP
0.86
MPC
1.5
ClinPred
0.99
D
GERP RS
2.1
Varity_R
0.77
gMVP
0.82

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: rs761451613; hg19: chr14-105517708; API