rs5853517

Positions:

• chr3-151339796-CT-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001393769.1(MED12L):​c.2251-10261del 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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MED12L	NM_001393769.1	c.2251-10261del		intron_variant		ENST00000687756.1
P2RY12	NM_022788.5	c.-15+799del		intron_variant		ENST00000302632.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RY12	ENST00000302632.4	c.-15+799del		intron_variant		1	NM_022788.5	P1
MED12L	ENST00000687756.1	c.2251-10261del		intron_variant			NM_001393769.1	A2

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

Gnomad4 AFR AF: 0.862

Gnomad4 AMR AF: 0.867

Gnomad4 ASJ AF: 0.879

Gnomad4 EAS AF: 0.848

Gnomad4 SAS AF: 0.900

Gnomad4 FIN AF: 0.842

Gnomad4 NFE AF: 0.832

Gnomad4 OTH AF: 0.874

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

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

Other links and lift over

dbSNP: rs5853517; hg19: chr3-151057584;