6-108663747-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_001455.4(FOXO3):c.914C>T(p.Ala305Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000753 in 1,461,426 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
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
FOXO3
NM_001455.4 missense
NM_001455.4 missense
Scores
8
10
Clinical Significance
Conservation
PhyloP100: 5.81
Genes affected
FOXO3 (HGNC:3821): (forkhead box O3) This gene belongs to the forkhead family of transcription factors which are characterized by a distinct forkhead domain. This gene likely functions as a trigger for apoptosis through expression of genes necessary for cell death. Translocation of this gene with the MLL gene is associated with secondary acute leukemia. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3327098).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXO3 | NM_001455.4 | c.914C>T | p.Ala305Val | missense_variant | 2/3 | ENST00000406360.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXO3 | ENST00000406360.2 | c.914C>T | p.Ala305Val | missense_variant | 2/3 | 1 | NM_001455.4 | P1 | |
FOXO3 | ENST00000343882.10 | c.914C>T | p.Ala305Val | missense_variant | 3/4 | 1 | P1 | ||
FOXO3 | ENST00000540898.1 | c.254C>T | p.Ala85Val | missense_variant | 2/3 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248522Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134666
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GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461426Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 726994
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GnomAD4 genome ? Cov.: 31
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31
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 29, 2021 | The c.914C>T (p.A305V) 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 914, causing the alanine (A) at amino acid position 305 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;L;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
P;P;.
Vest4
MutPred
Loss of catalytic residue at A305 (P = 0.1063);Loss of catalytic residue at A305 (P = 0.1063);.;
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at