X-71132767-CCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTT-CCTCTTCTCTTCTCTTCTCTTCTCTT

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_005120.3(MED12):c.4416-35_4416-16delCTTCTCTTCTCTTCTCTTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00813 in 653,407 control chromosomes in the GnomAD database, including 175 homozygotes. There are 1,283 hemizygotes in GnomAD. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.031 ( 104 hom., 483 hem., cov: 0)

Exomes 𝑓: 0.0044 ( 71 hom. 800 hem. )

Consequence

MED12
NM_005120.3 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.312

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

FG syndrome 1
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
MED12-related intellectual disability syndrome
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
X-linked intellectual disability with marfanoid habitus
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
blepharophimosis - intellectual disability syndrome, MKB type
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
cholestasis-pigmentary retinopathy-cleft palate syndrome
Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

MED12 links:

ENSG00000228427 (HGNC:):

ENSG00000228427 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant X-71132767-CCTCTTCTCTTCTCTTCTCTT-C is Benign according to our data. Variant chrX-71132767-CCTCTTCTCTTCTCTTCTCTT-C is described in CliVar as Likely_benign. Clinvar id is 418924.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-71132767-CCTCTTCTCTTCTCTTCTCTT-C is described in CliVar as Likely_benign. Clinvar id is 418924.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-71132767-CCTCTTCTCTTCTCTTCTCTT-C is described in CliVar as Likely_benign. Clinvar id is 418924.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-71132767-CCTCTTCTCTTCTCTTCTCTT-C is described in CliVar as Likely_benign. Clinvar id is 418924.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-71132767-CCTCTTCTCTTCTCTTCTCTT-C is described in CliVar as Likely_benign. Clinvar id is 418924.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-71132767-CCTCTTCTCTTCTCTTCTCTT-C is described in CliVar as Likely_benign. Clinvar id is 418924.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-71132767-CCTCTTCTCTTCTCTTCTCTT-C is described in CliVar as Likely_benign. Clinvar id is 418924.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-71132767-CCTCTTCTCTTCTCTTCTCTT-C is described in CliVar as Likely_benign. Clinvar id is 418924.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-71132767-CCTCTTCTCTTCTCTTCTCTT-C is described in CliVar as Likely_benign. Clinvar id is 418924.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-71132767-CCTCTTCTCTTCTCTTCTCTT-C is described in CliVar as Likely_benign. Clinvar id is 418924.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-71132767-CCTCTTCTCTTCTCTTCTCTT-C is described in CliVar as Likely_benign. Clinvar id is 418924.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-71132767-CCTCTTCTCTTCTCTTCTCTT-C is described in CliVar as Likely_benign. Clinvar id is 418924.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-71132767-CCTCTTCTCTTCTCTTCTCTT-C is described in CliVar as Likely_benign. Clinvar id is 418924.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-71132767-CCTCTTCTCTTCTCTTCTCTT-C is described in CliVar as Likely_benign. Clinvar id is 418924.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED12	NM_005120.3 link	c.4416-35_4416-16delCTTCTCTTCTCTTCTCTTCT		intron_variant	Intron 31 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.4416-77_4416-58delCTCTTCTCTTCTCTTCTCTT		intron_variant	Intron 31 of 44	1	NM_005120.3	ENSP00000363193.3		Q93074-1

Frequencies

GnomAD3 genomes

AF:

0.0311

AC:

2821

AN:

90595

Hom.:

104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0156

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00349

Gnomad SAS

AF:

0.0123

Gnomad FIN

AF:

0.00130

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00204

Gnomad OTH

AF:

0.0218

GnomAD4 exome

AF:

0.00441

AC:

2480

AN:

562772

Hom.:

AF XY:

0.00490

AC XY:

800

AN XY:

163126

show subpopulations

African (AFR)

AF:

0.0799

AC:

1183

AN:

14804

American (AMR)

AF:

0.00570

AC:

123

AN:

21585

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14203

East Asian (EAS)

AF:

0.00253

AC:

AN:

23313

South Asian (SAS)

AF:

0.00787

AC:

272

AN:

34549

European-Finnish (FIN)

AF:

0.00155

AC:

AN:

33470

Middle Eastern (MID)

AF:

0.00780

AC:

AN:

1922

European-Non Finnish (NFE)

AF:

0.00139

AC:

544

AN:

391564

Other (OTH)

AF:

0.00848

AC:

232

AN:

27362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.537

Heterozygous variant carriers

130

195

260

325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0312

AC:

2831

AN:

90635

Hom.:

104

Cov.:

AF XY:

0.0258

AC XY:

483

AN XY:

18741

show subpopulations

African (AFR)

AF:

0.104

AC:

2554

AN:

24595

American (AMR)

AF:

0.0155

AC:

125

AN:

8075

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2315

East Asian (EAS)

AF:

0.00389

AC:

AN:

2570

South Asian (SAS)

AF:

0.0112

AC:

AN:

1610

European-Finnish (FIN)

AF:

0.00130

AC:

AN:

3834

Middle Eastern (MID)

AF:

0.00

AC:

AN:

189

European-Non Finnish (NFE)

AF:

0.00204

AC:

AN:

45636

Other (OTH)

AF:

0.0215

AC:

AN:

1210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

183

274

366

457

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

352

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 23, 2018

GeneDx

Significance:Likely 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. -

MED12-related disorder

Benign:1

Feb 03, 2021

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

PhyloP100

0.31

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over