rs10521349

Positions:

chrX-71132567-T-C

Variant summary

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

The NM_005120.3(MED12):c.4415+29T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,162,723 control chromosomes in the GnomAD database, including 35,570 homozygotes. There are 105,229 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 2670 hom., 7057 hem., cov: 22)

Exomes 𝑓: 0.29 ( 32900 hom. 98172 hem. )

Consequence

MED12
NM_005120.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.381

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:

MED12 (HGNC:):

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=-0.85).

BP6

Variant X-71132567-T-C is Benign according to our data. Variant chrX-71132567-T-C is described in ClinVar as [Benign]. Clinvar id is 259637.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED12	NM_005120.3 linkuse as main transcript	c.4415+29T>C		intron_variant		ENST00000374080.8	NP_005111.2	Q93074-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED12	ENST00000374080.8 linkuse as main transcript	c.4415+29T>C		intron_variant		1	NM_005120.3	ENSP00000363193.3		Q93074-1

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

25139

AN:

110150

Hom.:

2672

Cov.:

AF XY:

0.217

AC XY:

7047

AN XY:

32492

show subpopulations

Gnomad AFR

AF:

0.0870

Gnomad AMI

AF:

0.392

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.401

Gnomad EAS

AF:

0.00254

Gnomad SAS

AF:

0.0914

Gnomad FIN

AF:

0.264

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.278

GnomAD3 exomes

AF:

0.227

AC:

26337

AN:

116232

Hom.:

2574

AF XY:

0.223

AC XY:

9099

AN XY:

40766

show subpopulations

Gnomad AFR exome

AF:

0.0809

Gnomad AMR exome

AF:

0.138

Gnomad ASJ exome

AF:

0.401

Gnomad EAS exome

AF:

0.00169

Gnomad SAS exome

AF:

0.117

Gnomad FIN exome

AF:

0.265

Gnomad NFE exome

AF:

0.322

Gnomad OTH exome

AF:

0.290

GnomAD4 exome

AF:

0.291

AC:

305906

AN:

1052520

Hom.:

32900

Cov.:

AF XY:

0.287

AC XY:

98172

AN XY:

342402

show subpopulations

Gnomad4 AFR exome

AF:

0.0836

Gnomad4 AMR exome

AF:

0.144

Gnomad4 ASJ exome

AF:

0.401

Gnomad4 EAS exome

AF:

0.000991

Gnomad4 SAS exome

AF:

0.122

Gnomad4 FIN exome

AF:

0.270

Gnomad4 NFE exome

AF:

0.320

Gnomad4 OTH exome

AF:

0.285

GnomAD4 genome

AF:

0.228

AC:

25139

AN:

110203

Hom.:

2670

Cov.:

AF XY:

0.217

AC XY:

7057

AN XY:

32555

show subpopulations

Gnomad4 AFR

AF:

0.0870

Gnomad4 AMR

AF:

0.199

Gnomad4 ASJ

AF:

0.401

Gnomad4 EAS

AF:

0.00255

Gnomad4 SAS

AF:

0.0928

Gnomad4 FIN

AF:

0.264

Gnomad4 NFE

AF:

0.320

Gnomad4 OTH

AF:

0.275

Alfa

AF:

0.294

Hom.:

14188

Bravo

AF:

0.218

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

- -

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

-0.85

CADD

Benign

0.93

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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