X-71118800-C-A
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4BP6_Very_StrongBS2
The NM_005120.3(MED12):c.46C>A(p.Arg16=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000191 in 1,206,141 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00010 ( 0 hom., 5 hem., cov: 20)
Exomes 𝑓: 0.000011 ( 0 hom. 3 hem. )
Consequence
MED12
NM_005120.3 synonymous
NM_005120.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.03
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 Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.11).
BP6
?
Variant X-71118800-C-A is Benign according to our data. Variant chrX-71118800-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1742533.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High Hemizygotes in GnomAd at 5 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MED12 | NM_005120.3 | c.46C>A | p.Arg16= | synonymous_variant | 1/45 | ENST00000374080.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED12 | ENST00000374080.8 | c.46C>A | p.Arg16= | synonymous_variant | 1/45 | 1 | NM_005120.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000101 AC: 11AN: 108577Hom.: 0 Cov.: 20 AF XY: 0.000162 AC XY: 5AN XY: 30855
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GnomAD3 exomes AF: 0.0000226 AC: 4AN: 176965Hom.: 0 AF XY: 0.0000153 AC XY: 1AN XY: 65183
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GnomAD4 exome AF: 0.0000109 AC: 12AN: 1097515Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 3AN XY: 363023
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 26, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
FG syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 02, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at