rs758467351
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_005120.3(MED12):c.1269G>A(p.Glu423=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,891 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )
Consequence
MED12
NM_005120.3 synonymous
NM_005120.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.916
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 Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant X-71122528-G-A is Benign according to our data. Variant chrX-71122528-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 458811.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.916 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MED12 | NM_005120.3 | c.1269G>A | p.Glu423= | synonymous_variant | 9/45 | ENST00000374080.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED12 | ENST00000374080.8 | c.1269G>A | p.Glu423= | synonymous_variant | 9/45 | 1 | NM_005120.3 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 23
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GnomAD3 exomes AF: 0.00000550 AC: 1AN: 181693Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67523
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GnomAD4 exome AF: 9.11e-7 AC: 1AN: 1097891Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 1AN XY: 363249
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GnomAD4 genome ? Cov.: 23
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
FG syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 18, 2017 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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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