rs768469811
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_030973.4(MED25):c.1973C>T(p.Thr658Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,612,198 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T658P) has been classified as Uncertain significance.
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.1973C>T | p.Thr658Ile | missense_variant | 17/18 | ENST00000312865.10 | |
MED25 | NM_001378355.1 | c.1973C>T | p.Thr658Ile | missense_variant | 17/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED25 | ENST00000312865.10 | c.1973C>T | p.Thr658Ile | missense_variant | 17/18 | 1 | NM_030973.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152184Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000206 AC: 5AN: 243076Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133176
GnomAD4 exome AF: 0.0000473 AC: 69AN: 1460014Hom.: 0 Cov.: 32 AF XY: 0.0000330 AC XY: 24AN XY: 726280
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152184Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74352
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 20, 2022 | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 658 of the MED25 protein (p.Thr658Ile). This variant is present in population databases (rs768469811, gnomAD 0.004%). 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: 543175). 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: "Deleterious"; PolyPhen-2: "Benign"; 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