rs1555801968
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_030973.4(MED25):c.393_394delinsCT(p.Met131_Arg132delinsIleCys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
MED25
NM_030973.4 missense
NM_030973.4 missense
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.58
Genes affected
MED25 (HGNC:28845): (mediator complex subunit 25) This gene encodes a component of the transcriptional coactivator complex termed the Mediator complex. This complex is required for transcription of most RNA polymerase II-dependent genes. The encoded protein plays a role in chromatin modification and in preinitiation complex assembly. Mutations in this gene are associated with Charcot-Marie-Tooth disease type 2B2. [provided by RefSeq, Apr 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MED25 | NM_030973.4 | c.393_394delinsCT | p.Met131_Arg132delinsIleCys | missense_variant | 4/18 | ENST00000312865.10 | |
MED25 | NM_001378355.1 | c.393_394delinsCT | p.Met131_Arg132delinsIleCys | missense_variant | 4/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED25 | ENST00000312865.10 | c.393_394delinsCT | p.Met131_Arg132delinsIleCys | missense_variant | 4/18 | 1 | NM_030973.4 | ||
MED25 | ENST00000595185.5 | c.393_394delinsCT | p.Met131_Arg132delinsIleCys | missense_variant | 4/7 | 1 | |||
MED25 | ENST00000538643.5 | c.181-1975_181-1974delinsCT | intron_variant | 1 | |||||
MED25 | ENST00000593767.3 | c.393_394delinsCT | p.Met131_Arg132delinsIleCys | missense_variant | 4/18 | 3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Charcot-Marie-Tooth disease type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 23, 2017 | This variant, c.393_394delGCinsCT, results in the deletion and insertion of 2 amino acids in the MED25 protein (p.Met131_Arg132delinsIleCys), but otherwise preserves the integrity of the reading frame. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the disrupted amino acids is currently unknown. In summary, this variant has uncertain impact on MED25 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals with a MED25-related disease. This variant is not present in population databases (ExAC no frequency). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at