Variant X-71132767-CCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTT-CCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTT 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.4416-25_4416-16dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0462 in 560,442 control chromosomes in the GnomAD database, including 1,355 homozygotes. There are 8,629 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 228 hom., 587 hem., cov: 0)

Exomes 𝑓: 0.046 ( 1355 hom. 8629 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: -0.294

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-C-CCTCTTCTCTT is Benign according to our data. Variant chrX-71132767-C-CCTCTTCTCTT is described in ClinVar as [Benign]. Clinvar id is 804026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED12	NM_005120.3 linkuse as main transcript	c.4416-25_4416-16dup		intron_variant		ENST00000374080.8	NP_005111.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED12	ENST00000374080.8 linkuse as main transcript	c.4416-25_4416-16dup		intron_variant		1	NM_005120.3	ENSP00000363193	P4	Q93074-1

Frequencies

GnomAD3 genomes

AF:

0.0550

AC:

4983

AN:

90554

Hom.:

229

Cov.:

AF XY:

0.0312

AC XY:

584

AN XY:

18704

show subpopulations

Gnomad AFR

AF:

0.0368

Gnomad AMI

AF:

0.00666

Gnomad AMR

AF:

0.0360

Gnomad ASJ

AF:

0.0674

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.0711

Gnomad FIN

AF:

0.0384

Gnomad MID

AF:

0.0667

Gnomad NFE

AF:

0.0655

Gnomad OTH

AF:

0.0488

GnomAD4 exome

AF:

0.0462

AC:

25873

AN:

560442

Hom.:

1355

AF XY:

0.0534

AC XY:

8629

AN XY:

161592

show subpopulations

Gnomad4 AFR exome

AF:

0.0277

Gnomad4 AMR exome

AF:

0.0338

Gnomad4 ASJ exome

AF:

0.0571

Gnomad4 EAS exome

AF:

0.113

Gnomad4 SAS exome

AF:

0.0818

Gnomad4 FIN exome

AF:

0.0477

Gnomad4 NFE exome

AF:

0.0393

Gnomad4 OTH exome

AF:

0.0555

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0550

AC:

4984

AN:

90594

Hom.:

228

Cov.:

AF XY:

0.0313

AC XY:

587

AN XY:

18744

show subpopulations

Gnomad4 AFR

AF:

0.0369

Gnomad4 AMR

AF:

0.0359

Gnomad4 ASJ

AF:

0.0674

Gnomad4 EAS

AF:

0.120

Gnomad4 SAS

AF:

0.0715

Gnomad4 FIN

AF:

0.0384

Gnomad4 NFE

AF:

0.0655

Gnomad4 OTH

AF:

0.0480

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

FG syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 14, 2019

- -

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