3-151382333-C-T

Variant names:

• chr3-151382333-C-T
• rs9289836
• NM_001393769.1:c.4591-323C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001393769.1(MED12L):​c.4591-323C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 151,934 control chromosomes in the GnomAD database, including 5,897 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (5897 hom., cov: 32)
• Consequence: MED12L NM_001393769.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.576
• Publications: 3 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, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393769.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED12L	NM_001393769.1	MANE Select	c.4591-323C>T		intron	N/A	NP_001380698.1	A0A8I5KX78
	P2RY12	NM_022788.5	MANE Select	c.-180+2359G>A		intron	N/A	NP_073625.1	Q9H244
	MED12L	NM_053002.6		c.4486-323C>T		intron	N/A	NP_443728.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED12L	ENST00000687756.1	MANE Select	c.4591-323C>T		intron	N/A	ENSP00000508695.1	A0A8I5KX78
	P2RY12	ENST00000302632.4	TSL:1 MANE Select	c.-180+2359G>A		intron	N/A	ENSP00000307259.4	Q9H244
	MED12L	ENST00000474524.5	TSL:1	c.4486-323C>T		intron	N/A	ENSP00000417235.1	Q86YW9-1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40534 AN: 151816 Hom.: 5890 Cov.: 32

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.267 AC: 40574 AN: 151934 Hom.: 5897 Cov.: 32 AF XY: 0.271 AC XY: 20143 AN XY: 74272

African (AFR) AF: 0.380 AC: 15740 AN: 41432

American (AMR) AF: 0.255 AC: 3898 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 490 AN: 3468

East Asian (EAS) AF: 0.291 AC: 1502 AN: 5170

South Asian (SAS) AF: 0.381 AC: 1834 AN: 4814

European-Finnish (FIN) AF: 0.219 AC: 2309 AN: 10548

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.208 AC: 14160 AN: 67934

Other (OTH) AF: 0.231 AC: 487 AN: 2110

Alfa AF: 0.164 Hom.: 462

Bravo AF: 0.272

Asia WGS AF: 0.322 AC: 1121 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.44
PhyloP100		-0.58
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: rs9289836; hg19: chr3-151100121;