3-151294790-C-T

Variant summary

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

The NM_023915.4(GPR87):​c.456G>A​(p.Met152Ile) 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. 13/21 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

GPR87
NM_023915.4 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.04
Variant links:
Genes affected
GPR87 (HGNC:4538): (G protein-coupled receptor 87) This gene encodes a G protein-coupled receptor and is located in a cluster of G protein-couple receptor genes on chromosome 3. The encoded protein has been shown to be overexpressed in lung squamous cell carcinoma (PMID:18057535) and regulated by p53 (PMID:19602589). [provided by RefSeq, Nov 2011]
MED12L (HGNC:16050): (mediator complex subunit 12L) The protein encoded by this gene is part of the Mediator complex, which is involved in transcriptional coactivation of nearly all RNA polymerase II-dependent genes. The Mediator complex links gene-specific transcriptional activators with the basal transcription machinery. [provided by RefSeq, May 2010]

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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=0.2970115).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPR87NM_023915.4 linkc.456G>A p.Met152Ile missense_variant Exon 3 of 3 ENST00000260843.5 NP_076404.3 Q9BY21
MED12LNM_001393769.1 linkc.2251-55269C>T intron_variant Intron 16 of 44 ENST00000687756.1 NP_001380698.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GPR87ENST00000260843.5 linkc.456G>A p.Met152Ile missense_variant Exon 3 of 3 1 NM_023915.4 ENSP00000260843.4 Q9BY21
MED12LENST00000687756.1 linkc.2251-55269C>T intron_variant Intron 16 of 44 NM_001393769.1 ENSP00000508695.1 A0A8I5KX78

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 25, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.456G>A (p.M152I) alteration is located in exon 3 (coding exon 2) of the GPR87 gene. This alteration results from a G to A substitution at nucleotide position 456, causing the methionine (M) at amino acid position 152 to be replaced by an isoleucine (I). 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
Uncertain
0.42
BayesDel_addAF
Benign
-0.030
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0099
T
Eigen
Benign
-0.35
Eigen_PC
Benign
-0.11
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.85
T
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.30
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.045
N
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
0.48
N
REVEL
Benign
0.15
Sift
Benign
0.55
T
Sift4G
Benign
0.64
T
Polyphen
0.019
B
Vest4
0.60
MutPred
0.36
Gain of catalytic residue at M152 (P = 0.0112);
MVP
0.62
MPC
0.28
ClinPred
0.82
D
GERP RS
4.6
Varity_R
0.37
gMVP
0.45

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: rs930287310; hg19: chr3-151012578; API