rs140083803
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_005120.3(MED12):c.6045-24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,208,727 control chromosomes in the GnomAD database, including 97 homozygotes. There are 5,416 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 0.012 ( 12 hom., 362 hem., cov: 22)
Exomes 𝑓: 0.015 ( 85 hom. 5054 hem. )
Consequence
MED12
NM_005120.3 intron
NM_005120.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0420
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant X-71140611-C-T is Benign according to our data. Variant chrX-71140611-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 259640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0115 (1278/110715) while in subpopulation NFE AF= 0.017 (898/52897). AF 95% confidence interval is 0.0161. There are 12 homozygotes in gnomad4. There are 362 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 12 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MED12 | NM_005120.3 | c.6045-24C>T | intron_variant | ENST00000374080.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED12 | ENST00000374080.8 | c.6045-24C>T | intron_variant | 1 | NM_005120.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0115 AC: 1278AN: 110661Hom.: 12 Cov.: 22 AF XY: 0.0110 AC XY: 362AN XY: 32867
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GnomAD3 exomes AF: 0.00987 AC: 1775AN: 179847Hom.: 2 AF XY: 0.00967 AC XY: 648AN XY: 67001
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GnomAD4 exome AF: 0.0146 AC: 16081AN: 1098012Hom.: 85 Cov.: 32 AF XY: 0.0139 AC XY: 5054AN XY: 363384
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GnomAD4 genome ? AF: 0.0115 AC: 1278AN: 110715Hom.: 12 Cov.: 22 AF XY: 0.0110 AC XY: 362AN XY: 32931
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 14, 2018 | 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. - |
Computational scores
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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