rs764789036
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBS1BS2
The NM_005120.3(MED12):c.6315_6320delACAGCA(p.Gln2106_Gln2107del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000162 in 1,159,273 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 58 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00020 ( 0 hom., 6 hem., cov: 23)
Exomes 𝑓: 0.00016 ( 0 hom. 52 hem. )
Consequence
MED12
NM_005120.3 disruptive_inframe_deletion
NM_005120.3 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.50
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 -17 ACMG points.
BP3
Nonframeshift variant in repetitive region in NM_005120.3
BP6
Variant X-71141265-GCAGCAA-G is Benign according to our data. Variant chrX-71141265-GCAGCAA-G is described in ClinVar as [Likely_benign]. Clinvar id is 458830.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 = 0.000202 (22/108870) while in subpopulation NFE AF= 0.000402 (21/52274). AF 95% confidence interval is 0.000268. There are 0 homozygotes in gnomad4. There are 6 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
High Hemizygotes in GnomAd4 at 6 XL gene
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000202 AC: 22AN: 108870Hom.: 0 Cov.: 23 AF XY: 0.000190 AC XY: 6AN XY: 31608
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GnomAD3 exomes AF: 0.000106 AC: 12AN: 113583Hom.: 0 AF XY: 0.0000738 AC XY: 3AN XY: 40659
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GnomAD4 exome AF: 0.000158 AC: 166AN: 1050403Hom.: 0 AF XY: 0.000152 AC XY: 52AN XY: 341557
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GnomAD4 genome AF: 0.000202 AC: 22AN: 108870Hom.: 0 Cov.: 23 AF XY: 0.000190 AC XY: 6AN XY: 31608
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 29, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | MED12: BS2 - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 17, 2017 | 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
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 12, 2024 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at