14-34713491-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_138638.5(CFL2):c.74C>T(p.Thr25Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,574 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T25A) has been classified as Uncertain significance.
Frequency
Consequence
NM_138638.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CFL2 | NM_138638.5 | c.74C>T | p.Thr25Ile | missense_variant | 2/4 | ENST00000298159.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFL2 | ENST00000298159.11 | c.74C>T | p.Thr25Ile | missense_variant | 2/4 | 1 | NM_138638.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250776Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135568
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461574Hom.: 0 Cov.: 33 AF XY: 0.00000963 AC XY: 7AN XY: 727096
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 05, 2017 | The T25I variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The T25I variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position where amino acids with similar properties to Threonine are tolerated across species. However, this variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In silico analysis predicts this variant is probably damaging to the protein structure/function. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at