chrX-71132767-CCTCTTCTCTTCTCTTCTCTTCTCTT-C
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1
The NM_005120.3(MED12):c.4416-40_4416-16del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.054 in 653,221 control chromosomes in the GnomAD database, including 1,214 homozygotes. There are 12,437 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.085 ( 344 hom., 1698 hem., cov: 0)
Exomes 𝑓: 0.049 ( 870 hom. 10739 hem. )
Consequence
MED12
NM_005120.3 intron
NM_005120.3 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.312
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 -10 ACMG points.
BP6
Variant X-71132767-CCTCTTCTCTTCTCTTCTCTTCTCTT-C is Benign according to our data. Variant chrX-71132767-CCTCTTCTCTTCTCTTCTCTTCTCTT-C is described in ClinVar as [Benign]. Clinvar id is 213614.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MED12 | NM_005120.3 | c.4416-40_4416-16del | intron_variant | ENST00000374080.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED12 | ENST00000374080.8 | c.4416-40_4416-16del | intron_variant | 1 | NM_005120.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0853 AC: 7723AN: 90564Hom.: 340 Cov.: 0 AF XY: 0.0903 AC XY: 1686AN XY: 18666
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GnomAD4 exome AF: 0.0489 AC: 27538AN: 562616Hom.: 870 AF XY: 0.0659 AC XY: 10739AN XY: 162986
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GnomAD4 genome AF: 0.0854 AC: 7742AN: 90605Hom.: 344 Cov.: 0 AF XY: 0.0908 AC XY: 1698AN XY: 18707
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, flagged submission | clinical testing | GeneDx | Apr 24, 2015 | 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 15, 2019 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at