Genetic Variant GPR87:p.Val165Ile (chr3-151294753-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_023915.4(GPR87):c.493G>A(p.Val165Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00393 in 1,614,134 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 15 hom. )

Consequence

GPR87
NM_023915.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.55

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]

GPR87 links:

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]

MED12L links:

ENSG00000286273 (HGNC:):

ENSG00000286273 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012078792).

BP6

Variant 3-151294753-C-T is Benign according to our data. Variant chr3-151294753-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2654231.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR87	NM_023915.4 link	c.493G>A	p.Val165Ile	missense_variant	Exon 3 of 3	ENST00000260843.5	NP_076404.3	Q9BY21
MED12L	NM_001393769.1 link	c.2251-55306C>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
GPR87	ENST00000260843.5 link	c.493G>A	p.Val165Ile	missense_variant	Exon 3 of 3	1	NM_023915.4	ENSP00000260843.4		Q9BY21
MED12L	ENST00000687756.1 link	c.2251-55306C>T		intron_variant	Intron 16 of 44		NM_001393769.1	ENSP00000508695.1		A0A8I5KX78

Frequencies

GnomAD3 genomes

AF:

0.00223

AC:

340

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00398

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00240

AC:

603

AN:

251292

Hom.:

AF XY:

0.00242

AC XY:

328

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00108

Gnomad FIN exome

AF:

0.000647

Gnomad NFE exome

AF:

0.00438

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00410

AC:

5999

AN:

1461840

Hom.:

Cov.:

AF XY:

0.00391

AC XY:

2844

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000985

Gnomad4 FIN exome

AF:

0.00112

Gnomad4 NFE exome

AF:

0.00496

Gnomad4 OTH exome

AF:

0.00450

GnomAD4 genome

AF:

0.00223

AC:

340

AN:

152294

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

151

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00398

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00359

Hom.:

Bravo

AF:

0.00235

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00419

AC:

ExAC

AF:

0.00268

AC:

326

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00382

EpiControl

AF:

0.00261

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ENSG00000286273: BS2; GPR87: BP4, BS2; MED12L: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.72

M_CAP

Benign

0.021

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.050

REVEL

Benign

0.20

Sift

Benign

0.72

Sift4G

Benign

0.67

Polyphen

0.66

Vest4

0.25

MVP

0.64

MPC

0.25

ClinPred

0.028

GERP RS

5.5

Varity_R

0.19

gMVP

0.59

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over