3-151294177-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_023915.4(GPR87):​c.1069G>T​(p.Asp357Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

GPR87
NM_023915.4 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.68
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPR87NM_023915.4 linkc.1069G>T p.Asp357Tyr missense_variant Exon 3 of 3 ENST00000260843.5 NP_076404.3 Q9BY21
MED12LNM_001393769.1 linkc.2251-55882C>A 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.1069G>T p.Asp357Tyr missense_variant Exon 3 of 3 1 NM_023915.4 ENSP00000260843.4 Q9BY21
MED12LENST00000687756.1 linkc.2251-55882C>A intron_variant Intron 16 of 44 NM_001393769.1 ENSP00000508695.1 A0A8I5KX78

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
24
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 29, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1069G>T (p.D357Y) alteration is located in exon 3 (coding exon 2) of the GPR87 gene. This alteration results from a G to T substitution at nucleotide position 1069, causing the aspartic acid (D) at amino acid position 357 to be replaced by a tyrosine (Y). 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
0.35
BayesDel_addAF
Benign
0.0052
T
BayesDel_noAF
Benign
-0.23
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.025
T
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.76
T
M_CAP
Benign
0.030
D
MetaRNN
Uncertain
0.60
D
MetaSVM
Benign
-0.68
T
MutationAssessor
Benign
0.0
N
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.19
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0030
D
Polyphen
0.98
D
Vest4
0.61
MutPred
0.40
Gain of glycosylation at Y353 (P = 0.0299);
MVP
0.81
MPC
0.28
ClinPred
0.85
D
GERP RS
5.2
Varity_R
0.26
gMVP
0.68

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-151011965; API