12-98515872-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001032283.3(TMPO):c.5C>T(p.Pro2Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,612,948 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001032283.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMPO | NM_001032283.3 | c.5C>T | p.Pro2Leu | missense_variant | Exon 1 of 9 | ENST00000556029.6 | NP_001027454.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460748Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726660
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74342
ClinVar
Submissions by phenotype
Loeys-Dietz syndrome 2 Uncertain:1
This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 2 of the TMPO protein (p.Pro2Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TMPO-related conditions. 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: "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