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

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_005120.3(MED12):c.4416-30_4416-16del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00573 in 653,305 control chromosomes in the GnomAD database, including 126 homozygotes. There are 833 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.024 ( 87 hom., 379 hem., cov: 0)

Exomes 𝑓: 0.0028 ( 39 hom. 454 hem. )

Consequence

MED12
NM_005120.3 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant X-71132767-CCTCTTCTCTTCTCTT-C is Benign according to our data. Variant chrX-71132767-CCTCTTCTCTTCTCTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 3059906.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-71132767-CCTCTTCTCTTCTCTT-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0774 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.4416-30_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.4416-30_4416-16del		intron_variant		1	NM_005120.3	P4	Q93074-1

Frequencies

GnomAD3 genomes

AF:

0.0237

AC:

2145

AN:

90599

Hom.:

Cov.:

AF XY:

0.0201

AC XY:

376

AN XY:

18699

show subpopulations

Gnomad AFR

AF:

0.0802

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00918

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00155

Gnomad SAS

AF:

0.00494

Gnomad FIN

AF:

0.000261

Gnomad MID

AF:

0.00476

Gnomad NFE

AF:

0.00151

Gnomad OTH

AF:

0.0168

GnomAD4 exome

AF:

0.00282

AC:

1589

AN:

562666

Hom.:

AF XY:

0.00278

AC XY:

454

AN XY:

163022

show subpopulations

Gnomad4 AFR exome

AF:

0.0552

Gnomad4 AMR exome

AF:

0.00389

Gnomad4 ASJ exome

AF:

0.000141

Gnomad4 EAS exome

AF:

0.000729

Gnomad4 SAS exome

AF:

0.00362

Gnomad4 FIN exome

AF:

0.000418

Gnomad4 NFE exome

AF:

0.000912

Gnomad4 OTH exome

AF:

0.00625

GnomAD4 genome

AF:

0.0238

AC:

2155

AN:

90639

Hom.:

Cov.:

AF XY:

0.0202

AC XY:

379

AN XY:

18739

show subpopulations

Gnomad4 AFR

AF:

0.0804

Gnomad4 AMR

AF:

0.00929

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00156

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.000261

Gnomad4 NFE

AF:

0.00151

Gnomad4 OTH

AF:

0.0165

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MED12-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 12, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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