Variant 3-151355245-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001393769.1(MED12L):c.2517+6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 1,590,704 control chromosomes in the GnomAD database, including 395,713 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 45424 hom., cov: 31)

Exomes 𝑓: 0.69 ( 350289 hom. )

Consequence

MED12L
NM_001393769.1 splice_region, intron

Scores

Splicing: ADA: 0.002986

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.661

Variant links:

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]

MED12L links:

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:):

MED12L links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 3-151355245-T-C is Benign according to our data. Variant chr3-151355245-T-C is described in ClinVar as [Benign]. Clinvar id is 1321163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED12L	NM_001393769.1 linkuse as main transcript	c.2517+6T>C		splice_region_variant, intron_variant		ENST00000687756.1	NP_001380698.1
P2RY12	NM_022788.5 linkuse as main transcript	c.-179-14485A>G		intron_variant		ENST00000302632.4	NP_073625.1	Q9H244A8K7T1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED12L	ENST00000687756.1 linkuse as main transcript	c.2517+6T>C		splice_region_variant, intron_variant			NM_001393769.1	ENSP00000508695.1		A0A8I5KX78
P2RY12	ENST00000302632.4 linkuse as main transcript	c.-179-14485A>G		intron_variant		1	NM_022788.5	ENSP00000307259.4		Q9H244

Frequencies

GnomAD3 genomes

AF:

0.765

AC:

116267

AN:

151978

Hom.:

45371

Cov.:

show subpopulations

Gnomad AFR

AF:

0.919

Gnomad AMI

AF:

0.689

Gnomad AMR

AF:

0.770

Gnomad ASJ

AF:

0.697

Gnomad EAS

AF:

0.854

Gnomad SAS

AF:

0.858

Gnomad FIN

AF:

0.740

Gnomad MID

AF:

0.797

Gnomad NFE

AF:

0.665

Gnomad OTH

AF:

0.773

GnomAD3 exomes

AF:

0.748

AC:

185309

AN:

247806

Hom.:

70382

AF XY:

0.745

AC XY:

99865

AN XY:

133976

show subpopulations

Gnomad AFR exome

AF:

0.926

Gnomad AMR exome

AF:

0.817

Gnomad ASJ exome

AF:

0.709

Gnomad EAS exome

AF:

0.849

Gnomad SAS exome

AF:

0.850

Gnomad FIN exome

AF:

0.735

Gnomad NFE exome

AF:

0.665

Gnomad OTH exome

AF:

0.728

GnomAD4 exome

AF:

0.694

AC:

998275

AN:

1438608

Hom.:

350289

Cov.:

AF XY:

0.698

AC XY:

500692

AN XY:

716958

show subpopulations

Gnomad4 AFR exome

AF:

0.930

Gnomad4 AMR exome

AF:

0.813

Gnomad4 ASJ exome

AF:

0.706

Gnomad4 EAS exome

AF:

0.843

Gnomad4 SAS exome

AF:

0.846

Gnomad4 FIN exome

AF:

0.727

Gnomad4 NFE exome

AF:

0.661

Gnomad4 OTH exome

AF:

0.722

GnomAD4 genome

AF:

0.765

AC:

116382

AN:

152096

Hom.:

45424

Cov.:

AF XY:

0.772

AC XY:

57423

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.919

Gnomad4 AMR

AF:

0.771

Gnomad4 ASJ

AF:

0.697

Gnomad4 EAS

AF:

0.855

Gnomad4 SAS

AF:

0.857

Gnomad4 FIN

AF:

0.740

Gnomad4 NFE

AF:

0.665

Gnomad4 OTH

AF:

0.771

Alfa

AF:

0.704

Hom.:

30013

Bravo

AF:

0.773

Asia WGS

AF:

0.824

AC:

2867

AN:

3478

EpiCase

AF:

0.675

EpiControl

AF:

0.676

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Nizon-Isidor syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0030

dbscSNV1_RF

Benign

0.17

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