chr3-151337857-T-C

Position:

chr3-151337857-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022788.5(P2RY12):c.989A>G(p.Glu330Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0041 in 1,614,130 control chromosomes in the GnomAD database, including 230 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.022 ( 113 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 117 hom. )

Consequence

P2RY12
NM_022788.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.625

Variant links:

Genes affected

P2RY12 (HGNC:18124): (purinergic receptor P2Y12) The product of this gene belongs to the family of G-protein coupled receptors. This family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides. This receptor is involved in platelet aggregation, and is a potential target for the treatment of thromboembolisms and other clotting disorders. Mutations in this gene are implicated in bleeding disorder, platelet type 8 (BDPLT8). Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

P2RY12 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:

MED12L (HGNC:):

MED12L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001743257).

BP6

Variant 3-151337857-T-C is Benign according to our data. Variant chr3-151337857-T-C is described in ClinVar as [Benign]. Clinvar id is 775916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.075 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RY12	NM_022788.5 linkuse as main transcript	c.989A>G	p.Glu330Gly	missense_variant	3/3	ENST00000302632.4	NP_073625.1	Q9H244A8K7T1
MED12L	NM_001393769.1 linkuse as main transcript	c.2251-12202T>C		intron_variant		ENST00000687756.1	NP_001380698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RY12	ENST00000302632.4 linkuse as main transcript	c.989A>G	p.Glu330Gly	missense_variant	3/3	1	NM_022788.5	ENSP00000307259.4		Q9H244
MED12L	ENST00000687756.1 linkuse as main transcript	c.2251-12202T>C		intron_variant			NM_001393769.1	ENSP00000508695.1		A0A8I5KX78

Frequencies

GnomAD3 genomes

AF:

0.0218

AC:

3313

AN:

152222

Hom.:

113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.0143

GnomAD3 exomes

AF:

0.00581

AC:

1459

AN:

251058

Hom.:

AF XY:

0.00435

AC XY:

591

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.0816

Gnomad AMR exome

AF:

0.00318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00225

AC:

3296

AN:

1461790

Hom.:

117

Cov.:

AF XY:

0.00191

AC XY:

1387

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.0826

Gnomad4 AMR exome

AF:

0.00385

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000549

Gnomad4 OTH exome

AF:

0.00472

GnomAD4 genome

AF:

0.0218

AC:

3327

AN:

152340

Hom.:

113

Cov.:

AF XY:

0.0208

AC XY:

1551

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0773

Gnomad4 AMR

AF:

0.00503

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.00426

Hom.:

Bravo

AF:

0.0253

ESP6500AA

AF:

0.0704

AC:

310

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00713

AC:

866

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -

P2RY12-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.6

DANN

Benign

0.73

DEOGEN2

Benign

0.22

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0097

LIST_S2

Benign

0.49

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.6

REVEL

Benign

0.024

Sift

Benign

0.44

Sift4G

Benign

0.32

Polyphen

0.0

Vest4

0.027

MVP

0.27

MPC

0.33

ClinPred

0.0024

GERP RS

-0.35

Varity_R

0.037

gMVP

0.24

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