rs5853517

Variant names:

• chr3-151339796-CT-C
• rs5853517
• NM_001393769.1:c.2251-10261delT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001393769.1(MED12L):​c.2251-10261delT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.85 (54763 hom., cov: 0)
• Consequence: MED12L NM_001393769.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 11 publications found

Genes affected

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]

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 Gene-Disease associations (from GenCC):

• platelet-type bleeding disorder 8

  Inheritance: AD, AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED12L	NM_001393769.1	c.2251-10261delT		intron_variant	Intron 16 of 44	ENST00000687756.1	NP_001380698.1
P2RY12	NM_022788.5	c.-15+799delA		intron_variant	Intron 2 of 2	ENST00000302632.4	NP_073625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED12L	ENST00000687756.1	c.2251-10262delT		intron_variant	Intron 16 of 44		NM_001393769.1	ENSP00000508695.1
P2RY12	ENST00000302632.4	c.-15+799delA		intron_variant	Intron 2 of 2	1	NM_022788.5	ENSP00000307259.4

Frequencies

GnomAD3 genomes AF: 0.849 AC: 128907 AN: 151896 Hom.: 54733 Cov.: 0

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.867

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.900

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.880

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.849 AC: 128991 AN: 152012 Hom.: 54763 Cov.: 0 AF XY: 0.851 AC XY: 63220 AN XY: 74292

African (AFR) AF: 0.862 AC: 35758 AN: 41500

American (AMR) AF: 0.867 AC: 13225 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.879 AC: 3049 AN: 3468

East Asian (EAS) AF: 0.848 AC: 4391 AN: 5176

South Asian (SAS) AF: 0.900 AC: 4342 AN: 4826

European-Finnish (FIN) AF: 0.842 AC: 8878 AN: 10550

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56532 AN: 67926

Other (OTH) AF: 0.874 AC: 1846 AN: 2112

Alfa AF: 0.843 Hom.: 6599

Bravo AF: 0.850

Asia WGS AF: 0.836 AC: 2902 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5853517; hg19: chr3-151057584;