Variant chrX-71118549-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000692304.1(MED12):c.-206A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.55 ( 12781 hom., 17441 hem., cov: 22)

Exomes 𝑓: 0.47 ( 25492 hom. 51828 hem. )

Failed GnomAD Quality Control

Consequence

MED12
ENST00000692304.1 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.46

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant X-71118549-A-G is Benign according to our data. Variant chrX-71118549-A-G is described in ClinVar as [Benign]. Clinvar id is 670932.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MED12	NM_005120.3 linkuse as main transcript			upstream_gene_variant		ENST00000374080.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED12	ENST00000374080.8 linkuse as main transcript			upstream_gene_variant		1	NM_005120.3	P4	Q93074-1

Frequencies

GnomAD3 genomes

AF:

0.550

AC:

60675

AN:

110285

Hom.:

12781

Cov.:

AF XY:

0.535

AC XY:

17383

AN XY:

32501

show subpopulations

Gnomad AFR

AF:

0.751

Gnomad AMI

AF:

0.493

Gnomad AMR

AF:

0.602

Gnomad ASJ

AF:

0.571

Gnomad EAS

AF:

0.325

Gnomad SAS

AF:

0.458

Gnomad FIN

AF:

0.383

Gnomad MID

AF:

0.626

Gnomad NFE

AF:

0.461

Gnomad OTH

AF:

0.574

GnomAD4 exome

AF:

0.471

AC:

156103

AN:

331561

Hom.:

25492

Cov.:

AF XY:

0.470

AC XY:

51828

AN XY:

110233

show subpopulations

Gnomad4 AFR exome

AF:

0.751

Gnomad4 AMR exome

AF:

0.606

Gnomad4 ASJ exome

AF:

0.576

Gnomad4 EAS exome

AF:

0.323

Gnomad4 SAS exome

AF:

0.476

Gnomad4 FIN exome

AF:

0.391

Gnomad4 NFE exome

AF:

0.458

Gnomad4 OTH exome

AF:

0.509

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.550

AC:

60731

AN:

110341

Hom.:

12781

Cov.:

AF XY:

0.536

AC XY:

17441

AN XY:

32567

show subpopulations

Gnomad4 AFR

AF:

0.751

Gnomad4 AMR

AF:

0.601

Gnomad4 ASJ

AF:

0.571

Gnomad4 EAS

AF:

0.325

Gnomad4 SAS

AF:

0.458

Gnomad4 FIN

AF:

0.383

Gnomad4 NFE

AF:

0.461

Gnomad4 OTH

AF:

0.581

Alfa

AF:

0.484

Hom.:

39625

Bravo

AF:

0.575

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.14

DANN

Benign

0.69

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