Variant X-71132767-CCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTT-CCTCTTCTCTTCTCTT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_005120.3(MED12):c.4416-45_4416-16del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 562,359 control chromosomes in the GnomAD database, including 15,649 homozygotes. There are 39,234 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 2582 hom., 5311 hem., cov: 0)

Exomes 𝑓: 0.22 ( 15649 hom. 39234 hem. )

Failed GnomAD Quality Control

Consequence

MED12
NM_005120.3 intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.312

Variant links:

Genes affected

MED12 (HGNC:11957): (mediator complex subunit 12) The initiation of transcription is controlled in part by a large protein assembly known as the preinitiation complex. A component of this preinitiation complex is a 1.2 MDa protein aggregate called Mediator. This Mediator component binds with a CDK8 subcomplex which contains the protein encoded by this gene, mediator complex subunit 12 (MED12), along with MED13, CDK8 kinase, and cyclin C. The CDK8 subcomplex modulates Mediator-polymerase II interactions and thereby regulates transcription initiation and reinitation rates. The MED12 protein is essential for activating CDK8 kinase. Defects in this gene cause X-linked Opitz-Kaveggia syndrome, also known as FG syndrome, and Lujan-Fryns syndrome. [provided by RefSeq, Aug 2009]

MED12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant X-71132767-CCTCTTCTCTTCTCTTCTCTTCTCTTCTCTT-C is Benign according to our data. Variant chrX-71132767-CCTCTTCTCTTCTCTTCTCTTCTCTTCTCTT-C is described in ClinVar as [Benign]. Clinvar id is 95251.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MED12	NM_005120.3 linkuse as main transcript	c.4416-45_4416-16del		intron_variant		ENST00000374080.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED12	ENST00000374080.8 linkuse as main transcript	c.4416-45_4416-16del		intron_variant		1	NM_005120.3	P4	Q93074-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

22704

AN:

90438

Hom.:

2584

Cov.:

AF XY:

0.286

AC XY:

5306

AN XY:

18552

FAILED QC

Gnomad AFR

AF:

0.0814

Gnomad AMI

AF:

0.417

Gnomad AMR

AF:

0.219

Gnomad ASJ

AF:

0.432

Gnomad EAS

AF:

0.00426

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.323

Gnomad MID

AF:

0.493

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.299

GnomAD4 exome

AF:

0.219

AC:

122883

AN:

562359

Hom.:

15649

AF XY:

0.241

AC XY:

39234

AN XY:

162735

show subpopulations

Gnomad4 AFR exome

AF:

0.0595

Gnomad4 AMR exome

AF:

0.128

Gnomad4 ASJ exome

AF:

0.358

Gnomad4 EAS exome

AF:

0.00275

Gnomad4 SAS exome

AF:

0.119

Gnomad4 FIN exome

AF:

0.288

Gnomad4 NFE exome

AF:

0.238

Gnomad4 OTH exome

AF:

0.244

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.251

AC:

22700

AN:

90479

Hom.:

2582

Cov.:

AF XY:

0.286

AC XY:

5311

AN XY:

18593

show subpopulations

Gnomad4 AFR

AF:

0.0813

Gnomad4 AMR

AF:

0.219

Gnomad4 ASJ

AF:

0.432

Gnomad4 EAS

AF:

0.00428

Gnomad4 SAS

AF:

0.118

Gnomad4 FIN

AF:

0.323

Gnomad4 NFE

AF:

0.347

Gnomad4 OTH

AF:

0.297

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 23, 2015	This variant was found in TAADV2-WO-FBN1-PANCARD,TAADV2-PANCARD -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 09, 2013	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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