chrX-71132767-CCTCTTCTCTT-C
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1
The NM_005120.3(MED12):c.4416-25_4416-16del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 652,215 control chromosomes in the GnomAD database, including 230 homozygotes. There are 2,887 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.042 ( 118 hom., 582 hem., cov: 0)
Exomes 𝑓: 0.013 ( 112 hom. 2305 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-CCTCTTCTCTT-C is Benign according to our data. Variant chrX-71132767-CCTCTTCTCTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 3055527.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-71132767-CCTCTTCTCTT-C is described in Lovd as [Likely_benign]. Variant chrX-71132767-CCTCTTCTCTT-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.098 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MED12 | NM_005120.3 | c.4416-25_4416-16del | intron_variant | ENST00000374080.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED12 | ENST00000374080.8 | c.4416-25_4416-16del | intron_variant | 1 | NM_005120.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0419 AC: 3796AN: 90594Hom.: 117 Cov.: 0 AF XY: 0.0311 AC XY: 581AN XY: 18700
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GnomAD4 exome AF: 0.0127 AC: 7152AN: 561581Hom.: 112 AF XY: 0.0142 AC XY: 2305AN XY: 162117
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GnomAD4 genome AF: 0.0419 AC: 3799AN: 90634Hom.: 118 Cov.: 0 AF XY: 0.0311 AC XY: 582AN XY: 18740
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
MED12-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 30, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at