6-108663615-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001455.4(FOXO3):c.782C>T(p.Thr261Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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. T261A) has been classified as Uncertain significance.
Frequency
Consequence
NM_001455.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXO3 | NM_001455.4 | c.782C>T | p.Thr261Ile | missense_variant | 2/3 | ENST00000406360.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXO3 | ENST00000406360.2 | c.782C>T | p.Thr261Ile | missense_variant | 2/3 | 1 | NM_001455.4 | P1 | |
FOXO3 | ENST00000343882.10 | c.782C>T | p.Thr261Ile | missense_variant | 3/4 | 1 | P1 | ||
FOXO3 | ENST00000540898.1 | c.122C>T | p.Thr41Ile | missense_variant | 2/3 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152202Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248678Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134758
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461250Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 726920
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152202Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74360
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 16, 2021 | The c.782C>T (p.T261I) alteration is located in exon 2 (coding exon 2) of the FOXO3 gene. This alteration results from a C to T substitution at nucleotide position 782, causing the threonine (T) at amino acid position 261 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at