dbSNP rs5853517: MED12L:c.2251-10261delT (chr3-151339796-CT-C) – ACMG Classification: Benign (-8 pts)

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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

platelet-type bleeding disorder 8
Inheritance: AR, AD Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics

P2RY12 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001393769.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MED12L	NM_001393769.1	MANE Select	c.2251-10261delT	intron	N/A	NP_001380698.1	A0A8I5KX78
P2RY12	NM_022788.5	MANE Select	c.-15+799delA	intron	N/A	NP_073625.1	Q9H244
MED12L	NM_053002.6		c.2146-10261delT	intron	N/A	NP_443728.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MED12L	ENST00000687756.1	MANE Select	c.2251-10262delT	intron	N/A	ENSP00000508695.1	A0A8I5KX78
P2RY12	ENST00000302632.4	TSL:1 MANE Select	c.-15+799delA	intron	N/A	ENSP00000307259.4	Q9H244
MED12L	ENST00000474524.5	TSL:1	c.2146-10262delT	intron	N/A	ENSP00000417235.1	Q86YW9-1

Frequencies

GnomAD3 genomes

AF:

0.849

AC:

128907

AN:

151896

Hom.:

54733

Cov.:

show subpopulations

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.:

AF XY:

0.851

AC XY:

63220

AN XY:

74292

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

976

1952

2928

3904

4880

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

892

1784

2676

3568

4460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over