X-71118708-A-G
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_005120.3(MED12):c.-47A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000972 in 1,028,849 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 20)
Exomes 𝑓: 9.7e-7 ( 0 hom. 0 hem. )
Consequence
MED12
NM_005120.3 5_prime_UTR
NM_005120.3 5_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.25
Publications
0 publications found
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 1Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
- MED12-related intellectual disability syndromeInheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
- X-linked intellectual disability with marfanoid habitusInheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
- blepharophimosis - intellectual disability syndrome, MKB typeInheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
- cholestasis-pigmentary retinopathy-cleft palate syndromeInheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
20
GnomAD4 exome AF: 9.72e-7 AC: 1AN: 1028849Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 312445 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1028849
Hom.:
Cov.:
23
AF XY:
AC XY:
0
AN XY:
312445
show subpopulations
African (AFR)
AF:
AC:
0
AN:
24810
American (AMR)
AF:
AC:
0
AN:
31836
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
18609
East Asian (EAS)
AF:
AC:
0
AN:
28413
South Asian (SAS)
AF:
AC:
0
AN:
50224
European-Finnish (FIN)
AF:
AC:
0
AN:
38472
Middle Eastern (MID)
AF:
AC:
0
AN:
3565
European-Non Finnish (NFE)
AF:
AC:
1
AN:
789362
Other (OTH)
AF:
AC:
0
AN:
43558
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
20
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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