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

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_005120.3(MED12):c.4416-25_4416-16del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 652,215 control chromosomes in the GnomAD database, including 230 homozygotes. There are 2,887 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.042 ( 118 hom., 582 hem., cov: 0)

Exomes 𝑓: 0.013 ( 112 hom. 2305 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 -10 ACMG points.

BP6

Variant X-71132767-CCTCTTCTCTT-C is Benign according to our data. Variant chrX-71132767-CCTCTTCTCTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 3055527.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-71132767-CCTCTTCTCTT-C is described in Lovd as [Likely_benign]. Variant chrX-71132767-CCTCTTCTCTT-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.098 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.4416-25_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.4416-25_4416-16del		intron_variant		1	NM_005120.3	P4	Q93074-1

Frequencies

GnomAD3 genomes

AF:

0.0419

AC:

3796

AN:

90594

Hom.:

117

Cov.:

AF XY:

0.0311

AC XY:

581

AN XY:

18700

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.00666

Gnomad AMR

AF:

0.0444

Gnomad ASJ

AF:

0.0337

Gnomad EAS

AF:

0.0190

Gnomad SAS

AF:

0.0148

Gnomad FIN

AF:

0.00261

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0161

Gnomad OTH

AF:

0.0403

GnomAD4 exome

AF:

0.0127

AC:

7152

AN:

561581

Hom.:

112

AF XY:

0.0142

AC XY:

2305

AN XY:

162117

show subpopulations

Gnomad4 AFR exome

AF:

0.0727

Gnomad4 AMR exome

AF:

0.0269

Gnomad4 ASJ exome

AF:

0.0292

Gnomad4 EAS exome

AF:

0.0192

Gnomad4 SAS exome

AF:

0.0180

Gnomad4 FIN exome

AF:

0.00327

Gnomad4 NFE exome

AF:

0.00848

Gnomad4 OTH exome

AF:

0.0206

GnomAD4 genome

AF:

0.0419

AC:

3799

AN:

90634

Hom.:

118

Cov.:

AF XY:

0.0311

AC XY:

582

AN XY:

18740

show subpopulations

Gnomad4 AFR

AF:

0.101

Gnomad4 AMR

AF:

0.0444

Gnomad4 ASJ

AF:

0.0337

Gnomad4 EAS

AF:

0.0191

Gnomad4 SAS

AF:

0.0149

Gnomad4 FIN

AF:

0.00261

Gnomad4 NFE

AF:

0.0161

Gnomad4 OTH

AF:

0.0388

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

Oct 30, 2020

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