rs369707406
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_030973.4(MED25):c.1786G>A(p.Val596Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000553 in 1,609,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V596V) has been classified as Likely benign.
Frequency
Consequence
NM_030973.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MED25 | NM_030973.4 | c.1786G>A | p.Val596Ile | missense_variant | 16/18 | ENST00000312865.10 | |
MED25 | NM_001378355.1 | c.1786G>A | p.Val596Ile | missense_variant | 16/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED25 | ENST00000312865.10 | c.1786G>A | p.Val596Ile | missense_variant | 16/18 | 1 | NM_030973.4 |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152144Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000629 AC: 15AN: 238484Hom.: 0 AF XY: 0.0000688 AC XY: 9AN XY: 130778
GnomAD4 exome AF: 0.0000528 AC: 77AN: 1457402Hom.: 0 Cov.: 32 AF XY: 0.0000634 AC XY: 46AN XY: 725034
GnomAD4 genome AF: 0.0000788 AC: 12AN: 152262Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74446
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 596 of the MED25 protein (p.Val596Ile). This variant is present in population databases (rs369707406, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MED25-related conditions. ClinVar contains an entry for this variant (Variation ID: 575396). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at