X-71119648-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005120.3(MED12):c.205-38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 1,195,049 control chromosomes in the GnomAD database, including 36,042 homozygotes. There are 107,131 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 2609 hom., 7062 hem., cov: 23)

Exomes 𝑓: 0.29 ( 33433 hom. 100069 hem. )

Consequence

MED12
NM_005120.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.375

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant X-71119648-C-T is Benign according to our data. Variant chrX-71119648-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 259633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED12	NM_005120.3 link	c.205-38C>T		intron_variant	Intron 2 of 44	ENST00000374080.8	NP_005111.2	Q93074-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED12	ENST00000374080.8 link	c.205-38C>T		intron_variant	Intron 2 of 44	1	NM_005120.3	ENSP00000363193.3		Q93074-1

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

24462

AN:

111785

Hom.:

2611

Cov.:

AF XY:

0.208

AC XY:

7059

AN XY:

34003

show subpopulations

Gnomad AFR

AF:

0.0558

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.197

Gnomad ASJ

AF:

0.405

Gnomad EAS

AF:

0.00279

Gnomad SAS

AF:

0.0931

Gnomad FIN

AF:

0.268

Gnomad MID

AF:

0.457

Gnomad NFE

AF:

0.319

Gnomad OTH

AF:

0.266

GnomAD3 exomes

AF:

0.221

AC:

37402

AN:

169442

Hom.:

3667

AF XY:

0.223

AC XY:

12675

AN XY:

56748

show subpopulations

Gnomad AFR exome

AF:

0.0509

Gnomad AMR exome

AF:

0.128

Gnomad ASJ exome

AF:

0.406

Gnomad EAS exome

AF:

0.00137

Gnomad SAS exome

AF:

0.111

Gnomad FIN exome

AF:

0.265

Gnomad NFE exome

AF:

0.314

Gnomad OTH exome

AF:

0.291

GnomAD4 exome

AF:

0.288

AC:

311631

AN:

1083212

Hom.:

33433

Cov.:

AF XY:

0.286

AC XY:

100069

AN XY:

350490

show subpopulations

Gnomad4 AFR exome

AF:

0.0526

Gnomad4 AMR exome

AF:

0.135

Gnomad4 ASJ exome

AF:

0.404

Gnomad4 EAS exome

AF:

0.000964

Gnomad4 SAS exome

AF:

0.120

Gnomad4 FIN exome

AF:

0.269

Gnomad4 NFE exome

AF:

0.321

Gnomad4 OTH exome

AF:

0.282

GnomAD4 genome

AF:

0.219

AC:

24454

AN:

111837

Hom.:

2609

Cov.:

AF XY:

0.207

AC XY:

7062

AN XY:

34065

show subpopulations

Gnomad4 AFR

AF:

0.0557

Gnomad4 AMR

AF:

0.196

Gnomad4 ASJ

AF:

0.405

Gnomad4 EAS

AF:

0.00280

Gnomad4 SAS

AF:

0.0941

Gnomad4 FIN

AF:

0.268

Gnomad4 NFE

AF:

0.319

Gnomad4 OTH

AF:

0.264

Alfa

AF:

0.214

Hom.:

1815

Bravo

AF:

0.208

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

X-linked intellectual disability with marfanoid habitus

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

FG syndrome 1

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Blepharophimosis - intellectual disability syndrome, MKB type

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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