3-151369849-C-T

Position:

• chr3-151369849-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001393769.1(MED12L):​c.3664+300C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 151,968 control chromosomes in the GnomAD database, including 6,365 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 (6365 hom., cov: 31)
• Consequence: MED12L NM_001393769.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED12L	NM_001393769.1	c.3664+300C>T		intron_variant		ENST00000687756.1	NP_001380698.1
P2RY12	NM_022788.5	c.-180+14843G>A		intron_variant		ENST00000302632.4	NP_073625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED12L	ENST00000687756.1	c.3664+300C>T		intron_variant			NM_001393769.1	ENSP00000508695.1
P2RY12	ENST00000302632.4	c.-180+14843G>A		intron_variant		1	NM_022788.5	ENSP00000307259.4

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40378 AN: 151850 Hom.: 6347 Cov.: 31

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.266 AC: 40443 AN: 151968 Hom.: 6365 Cov.: 31 AF XY: 0.259 AC XY: 19264 AN XY: 74284

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.265

Alfa AF: 0.107 Hom.: 153

Bravo AF: 0.277

Asia WGS AF: 0.175 AC: 612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.48

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: rs7634096; hg19: chr3-151087637;