rs1555802134
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_030973.4(MED25):c.547G>A(p.Val183Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
MED25
NM_030973.4 missense
NM_030973.4 missense
Scores
2
8
4
Clinical Significance
Conservation
PhyloP100: 3.19
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.30420852).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MED25 | NM_030973.4 | c.547G>A | p.Val183Met | missense_variant | 6/18 | ENST00000312865.10 | |
MED25 | NM_001378355.1 | c.547G>A | p.Val183Met | missense_variant | 6/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED25 | ENST00000312865.10 | c.547G>A | p.Val183Met | missense_variant | 6/18 | 1 | NM_030973.4 | ||
MED25 | ENST00000595185.5 | c.547G>A | p.Val183Met | missense_variant | 6/7 | 1 | |||
MED25 | ENST00000538643.5 | c.181-704G>A | intron_variant | 1 | |||||
MED25 | ENST00000593767.3 | c.547G>A | p.Val183Met | missense_variant | 6/18 | 3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1448288Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 719630
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1448288
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
719630
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
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 | Jun 17, 2017 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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). This sequence change replaces valine with methionine at codon 183 of the MED25 protein (p.Val183Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T;T;T
Polyphen
0.97
.;D;.;.
Vest4
MutPred
Gain of disorder (P = 0.12);Gain of disorder (P = 0.12);Gain of disorder (P = 0.12);Gain of disorder (P = 0.12);
MVP
MPC
1.1
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at