Variant rs2075790 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005120.3(MED12):c.2422+30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,059,878 control chromosomes in the GnomAD database, including 6,235 homozygotes. There are 46,414 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 726 hom., 3121 hem., cov: 18)

Exomes 𝑓: 0.14 ( 5509 hom. 43293 hem. )

Consequence

MED12
NM_005120.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.236

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant X-71125743-C-T is Benign according to our data. Variant chrX-71125743-C-T is described in ClinVar as [Benign]. Clinvar id is 259634.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.215 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.2422+30C>T		intron_variant		ENST00000374080.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED12	ENST00000374080.8 linkuse as main transcript	c.2422+30C>T		intron_variant		1	NM_005120.3	P4	Q93074-1

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

13256

AN:

101861

Hom.:

722

Cov.:

AF XY:

0.119

AC XY:

3111

AN XY:

26105

show subpopulations

Gnomad AFR

AF:

0.164

Gnomad AMI

AF:

0.0233

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.0928

Gnomad EAS

AF:

0.132

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.112

Gnomad MID

AF:

0.119

Gnomad NFE

AF:

0.118

Gnomad OTH

AF:

0.115

GnomAD3 exomes

AF:

0.133

AC:

23533

AN:

176424

Hom.:

1104

AF XY:

0.143

AC XY:

8938

AN XY:

62670

show subpopulations

Gnomad AFR exome

AF:

0.174

Gnomad AMR exome

AF:

0.100

Gnomad ASJ exome

AF:

0.0938

Gnomad EAS exome

AF:

0.154

Gnomad SAS exome

AF:

0.244

Gnomad FIN exome

AF:

0.121

Gnomad NFE exome

AF:

0.116

Gnomad OTH exome

AF:

0.115

GnomAD4 exome

AF:

0.136

AC:

129921

AN:

957961

Hom.:

5509

Cov.:

AF XY:

0.159

AC XY:

43293

AN XY:

272939

show subpopulations

Gnomad4 AFR exome

AF:

0.180

Gnomad4 AMR exome

AF:

0.102

Gnomad4 ASJ exome

AF:

0.102

Gnomad4 EAS exome

AF:

0.130

Gnomad4 SAS exome

AF:

0.235

Gnomad4 FIN exome

AF:

0.132

Gnomad4 NFE exome

AF:

0.130

Gnomad4 OTH exome

AF:

0.143

GnomAD4 genome

AF:

0.130

AC:

13270

AN:

101917

Hom.:

726

Cov.:

AF XY:

0.119

AC XY:

3121

AN XY:

26163

show subpopulations

Gnomad4 AFR

AF:

0.164

Gnomad4 AMR

AF:

0.103

Gnomad4 ASJ

AF:

0.0928

Gnomad4 EAS

AF:

0.132

Gnomad4 SAS

AF:

0.233

Gnomad4 FIN

AF:

0.112

Gnomad4 NFE

AF:

0.118

Gnomad4 OTH

AF:

0.124

Alfa

AF:

0.125

Hom.:

1360

Bravo

AF:

0.129

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

X-linked intellectual disability with marfanoid habitus

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

FG syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Blepharophimosis - intellectual disability syndrome, MKB type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

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