Genetic Variant GPR132:p.Glu346Lys (chr14-105051101-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013345.4(GPR132):c.1036G>A(p.Glu346Lys) 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 benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

GPR132
NM_013345.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.224

Publications

0 publications found

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:

LINC02298 (HGNC:53216): (long intergenic non-protein coding RNA 2298)

LINC02298 links:

LOC124903398 (HGNC:):

LOC124903398 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07584944).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013345.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPR132	NM_013345.4	MANE Select	c.1036G>A	p.Glu346Lys	missense	Exon 4 of 4	NP_037477.1	Q9UNW8-1
GPR132	NM_001278694.2		c.1036G>A	p.Glu346Lys	missense	Exon 5 of 5	NP_001265623.1	Q9UNW8-1
GPR132	NM_001278695.2		c.1009G>A	p.Glu337Lys	missense	Exon 3 of 3	NP_001265624.1	Q9UNW8-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPR132	ENST00000329797.8	TSL:1 MANE Select	c.1036G>A	p.Glu346Lys	missense	Exon 4 of 4	ENSP00000328818.3	Q9UNW8-1
GPR132	ENST00000392585.2	TSL:1	c.1009G>A	p.Glu337Lys	missense	Exon 3 of 3	ENSP00000376364.2	Q9UNW8-3
GPR132	ENST00000551869.1	TSL:1	n.*1062G>A		non_coding_transcript_exon	Exon 3 of 3	ENSP00000448513.1	F8VRH8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.66

M_CAP

Benign

0.018

MetaRNN

Benign

0.076

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PhyloP100

-0.22

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.91

REVEL

Benign

0.0020

Sift

Benign

0.13

Sift4G

Benign

0.12

Polyphen

0.096

Vest4

0.096

MutPred

0.37

Gain of ubiquitination at E346 (P = 0.0051)

MVP

0.47

MPC

1.3

ClinPred

0.22

GERP RS

2.6

Varity_R

0.096

gMVP

0.38

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over