NM_052963.3:c.1597C>T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_052963.3(TOP1MT):c.1597C>T(p.Gln533*) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000761 in 1,603,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_052963.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000388 AC: 59AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000807 AC: 19AN: 235534Hom.: 0 AF XY: 0.0000546 AC XY: 7AN XY: 128244
GnomAD4 exome AF: 0.0000434 AC: 63AN: 1450906Hom.: 0 Cov.: 37 AF XY: 0.0000277 AC XY: 20AN XY: 721246
GnomAD4 genome AF: 0.000387 AC: 59AN: 152320Hom.: 0 Cov.: 32 AF XY: 0.000349 AC XY: 26AN XY: 74496
ClinVar
Submissions by phenotype
not provided Uncertain:1
This variant has not been reported in the literature in individuals affected with TOP1MT-related conditions. This variant is present in population databases (rs149953316, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This sequence change creates a premature translational stop signal (p.Gln533*) in the TOP1MT gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in TOP1MT cause disease. 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