rs766775649
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP3
The NM_005120.3(MED12):c.6300_6308del(p.Gln2113_Gln2115del) variant causes a inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 9.5e-7 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control
Consequence
MED12
NM_005120.3 inframe_deletion
NM_005120.3 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.44
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP3
?
Nonframeshift variant in repetitive region in NM_005120.3
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MED12 | NM_005120.3 | c.6300_6308del | p.Gln2113_Gln2115del | inframe_deletion | 43/45 | ENST00000374080.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED12 | ENST00000374080.8 | c.6300_6308del | p.Gln2113_Gln2115del | inframe_deletion | 43/45 | 1 | NM_005120.3 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.53e-7 AC: 1AN: 1049299Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 340919
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
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1
AN:
1049299
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0
AN XY:
340919
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GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
FG syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 04, 2020 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals with MED12-related conditions. This variant is not present in population databases (ExAC no frequency). This variant, c.6300_6308del, results in the deletion of 3 amino acid(s) of the MED12 protein (p.Gln2113_Gln2115del), but otherwise preserves the integrity of the reading frame. - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at