3-151294477-C-T

Variant summary

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

The NM_023915.4(GPR87):​c.769G>A​(p.Val257Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,614,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

GPR87
NM_023915.4 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.05
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]

Genome browser will be placed here

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=0.27884185).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPR87NM_023915.4 linkc.769G>A p.Val257Ile missense_variant Exon 3 of 3 ENST00000260843.5 NP_076404.3 Q9BY21
MED12LNM_001393769.1 linkc.2251-55582C>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.769G>A p.Val257Ile missense_variant Exon 3 of 3 1 NM_023915.4 ENSP00000260843.4 Q9BY21
MED12LENST00000687756.1 linkc.2251-55582C>T intron_variant Intron 16 of 44 NM_001393769.1 ENSP00000508695.1 A0A8I5KX78

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152208
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250806
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135522
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:
0.00000884
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000889
AC:
13
AN:
1461886
Hom.:
0
Cov.:
34
AF XY:
0.00000825
AC XY:
6
AN XY:
727244
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152208
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000189
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 17, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.769G>A (p.V257I) 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 769, causing the valine (V) at amino acid position 257 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
Benign
0.19
BayesDel_addAF
Benign
0.0047
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.011
T
Eigen
Uncertain
0.28
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.72
T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.28
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.2
L
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-0.17
N
REVEL
Benign
0.20
Sift
Benign
0.94
T
Sift4G
Benign
0.58
T
Polyphen
0.97
D
Vest4
0.34
MVP
0.42
MPC
0.25
ClinPred
0.42
T
GERP RS
5.5
Varity_R
0.14
gMVP
0.40

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: rs374834030; hg19: chr3-151012265; API