X-71130097-A-C
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_005120.3(MED12):āc.3930A>Cā(p.Pro1310=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 1,206,739 control chromosomes in the GnomAD database, including 36,144 homozygotes. There are 108,959 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.22 ( 2601 hom., 7027 hem., cov: 24)
Exomes š: 0.29 ( 33543 hom. 101932 hem. )
Consequence
MED12
NM_005120.3 synonymous
NM_005120.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.08
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant X-71130097-A-C is Benign according to our data. Variant chrX-71130097-A-C is described in ClinVar as [Benign]. Clinvar id is 95248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-71130097-A-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-1.08 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MED12 | NM_005120.3 | c.3930A>C | p.Pro1310= | synonymous_variant | 28/45 | ENST00000374080.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED12 | ENST00000374080.8 | c.3930A>C | p.Pro1310= | synonymous_variant | 28/45 | 1 | NM_005120.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.218 AC: 24407AN: 111958Hom.: 2603 Cov.: 24 AF XY: 0.206 AC XY: 7024AN XY: 34148
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GnomAD3 exomes AF: 0.220 AC: 38184AN: 173323Hom.: 3695 AF XY: 0.223 AC XY: 13321AN XY: 59861
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GnomAD4 exome AF: 0.287 AC: 314096AN: 1094726Hom.: 33543 Cov.: 34 AF XY: 0.283 AC XY: 101932AN XY: 360392
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GnomAD4 genome AF: 0.218 AC: 24399AN: 112013Hom.: 2601 Cov.: 24 AF XY: 0.205 AC XY: 7027AN XY: 34213
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ClinVar
Significance: Benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 14, 2014 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
X-linked intellectual disability with marfanoid habitus Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 30, 2014 | This alteration is classified as 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 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
FG syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Blepharophimosis - intellectual disability syndrome, MKB type Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at