GeneBe

rs56658066

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005120.3(MED12):​c.4416-60_4416-16delCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000022 ( 0 hom., 1 hem., cov: 0)
Exomes 𝑓: 0.000041 ( 0 hom. 7 hem. )
Failed GnomAD Quality Control

Consequence

MED12
NM_005120.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MED12NM_005120.3 linkc.4416-60_4416-16delCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCT 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
MED12ENST00000374080.8 linkc.4416-77_4416-33delCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTT intron_variant Intron 31 of 44 1 NM_005120.3 ENSP00000363193.3 Q93074-1

Frequencies

GnomAD3 genomes
AF:
0.0000221
AC:
2
AN:
90626
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0000407
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000219
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000409
AC:
23
AN:
562803
Hom.:
0
AF XY:
0.0000429
AC XY:
7
AN XY:
163155
show subpopulations
African (AFR)
AF:
0.0000675
AC:
1
AN:
14814
American (AMR)
AF:
0.00
AC:
0
AN:
21585
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
14203
East Asian (EAS)
AF:
0.00
AC:
0
AN:
23314
South Asian (SAS)
AF:
0.00
AC:
0
AN:
34554
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
33470
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
1922
European-Non Finnish (NFE)
AF:
0.0000536
AC:
21
AN:
391577
Other (OTH)
AF:
0.0000365
AC:
1
AN:
27364
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.609
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
2
4
6
8
10
<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:
0.0000221
AC:
2
AN:
90626
Hom.:
0
Cov.:
0
AF XY:
0.0000535
AC XY:
1
AN XY:
18708
show subpopulations
African (AFR)
AF:
0.0000407
AC:
1
AN:
24570
American (AMR)
AF:
0.00
AC:
0
AN:
8062
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2315
East Asian (EAS)
AF:
0.00
AC:
0
AN:
2580
South Asian (SAS)
AF:
0.00
AC:
0
AN:
1620
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
3833
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
210
European-Non Finnish (NFE)
AF:
0.0000219
AC:
1
AN:
45645
Other (OTH)
AF:
0.00
AC:
0
AN:
1190
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Hom
Variant carriers
0
2
4
6
8
10
<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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.31

Splicing

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

Publications

Other links and lift over

dbSNP: rs56658066; hg19: chrX-70352617; API