rs1015978148
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_030973.4(MED25):c.802G>A(p.Val268Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000318 in 1,603,708 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 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. V268V) 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.802G>A | p.Val268Ile | missense_variant | 7/18 | ENST00000312865.10 | |
MED25 | NM_001378355.1 | c.802G>A | p.Val268Ile | missense_variant | 7/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED25 | ENST00000312865.10 | c.802G>A | p.Val268Ile | missense_variant | 7/18 | 1 | NM_030973.4 | ||
MED25 | ENST00000538643.5 | c.181-310G>A | intron_variant | 1 | |||||
MED25 | ENST00000595185.5 | c.688+253G>A | intron_variant | 1 | |||||
MED25 | ENST00000593767.3 | c.802G>A | p.Val268Ile | missense_variant | 7/18 | 3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000264 AC: 4AN: 151298Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000419 AC: 10AN: 238530Hom.: 0 AF XY: 0.0000537 AC XY: 7AN XY: 130422
GnomAD4 exome AF: 0.0000324 AC: 47AN: 1452410Hom.: 1 Cov.: 31 AF XY: 0.0000332 AC XY: 24AN XY: 721818
GnomAD4 genome ? AF: 0.0000264 AC: 4AN: 151298Hom.: 0 Cov.: 32 AF XY: 0.0000271 AC XY: 2AN XY: 73876
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2022 | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 268 of the MED25 protein (p.Val268Ile). This variant is present in population databases (no rsID available, gnomAD 0.03%). 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: 575416). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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