rs5030617
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_005120.3(MED12):c.3354+27G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,207,848 control chromosomes in the GnomAD database, including 7,017 homozygotes. There are 51,121 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.15 ( 1078 hom., 4491 hem., cov: 21)
Exomes 𝑓: 0.12 ( 5939 hom. 46630 hem. )
Consequence
MED12
NM_005120.3 intron
NM_005120.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.16
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-71128467-G-C is Benign according to our data. Variant chrX-71128467-G-C is described in ClinVar as [Benign]. Clinvar id is 259636.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MED12 | NM_005120.3 | c.3354+27G>C | intron_variant | ENST00000374080.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED12 | ENST00000374080.8 | c.3354+27G>C | intron_variant | 1 | NM_005120.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.150 AC: 16520AN: 110103Hom.: 1075 Cov.: 21 AF XY: 0.138 AC XY: 4477AN XY: 32377
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GnomAD3 exomes AF: 0.138 AC: 24941AN: 181332Hom.: 1251 AF XY: 0.142 AC XY: 9549AN XY: 67212
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GnomAD4 exome AF: 0.124 AC: 136413AN: 1097691Hom.: 5939 Cov.: 33 AF XY: 0.128 AC XY: 46630AN XY: 363125
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GnomAD4 genome ? AF: 0.150 AC: 16534AN: 110157Hom.: 1078 Cov.: 21 AF XY: 0.138 AC XY: 4491AN XY: 32441
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
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 | - - |
FG syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 26, 2018 | - - |
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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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at