4-105234058-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001127208.3(TET2):c.116C>T(p.Pro39Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001127208.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TET2 | NM_001127208.3 | c.116C>T | p.Pro39Leu | missense_variant | Exon 3 of 11 | ENST00000380013.9 | NP_001120680.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250928Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135598
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461784Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 727188
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74320
ClinVar
Submissions by phenotype
not specified Uncertain:1
The p.P39L variant (also known as c.116C>T), located in coding exon 1 of the TET2 gene, results from a C to T substitution at nucleotide position 116. The proline at codon 39 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. -
not provided Uncertain:1
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. 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"). This variant has not been reported in the literature in individuals affected with TET2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.008%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 39 of the TET2 protein (p.Pro39Leu). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at