chr14-89412350-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005197.4(FOXN3):c.127T>G(p.Phe43Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Consequence
FOXN3
NM_005197.4 missense
NM_005197.4 missense
Scores
1
3
14
Clinical Significance
Conservation
PhyloP100: 3.38
Genes affected
FOXN3 (HGNC:1928): (forkhead box N3) This gene is a member of the forkhead/winged helix transcription factor family. Checkpoints are eukaryotic DNA damage-inducible cell cycle arrests at G1 and G2. Checkpoint suppressor 1 suppresses multiple yeast checkpoint mutations including mec1, rad9, rad53 and dun1 by activating a MEC1-independent checkpoint pathway. Alternative splicing is observed at the locus, resulting in distinct isoforms. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.15973648).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXN3 | NM_005197.4 | c.127T>G | p.Phe43Val | missense_variant | 2/6 | ENST00000557258.6 | |
FOXN3 | NM_001085471.2 | c.127T>G | p.Phe43Val | missense_variant | 2/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXN3 | ENST00000557258.6 | c.127T>G | p.Phe43Val | missense_variant | 2/6 | 1 | NM_005197.4 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
Bravo
AF:
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 | Jun 03, 2022 | The c.127T>G (p.F43V) alteration is located in exon 2 (coding exon 1) of the FOXN3 gene. This alteration results from a T to G substitution at nucleotide position 127, causing the phenylalanine (F) at amino acid position 43 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
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T;.;.;.;T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
M;M;M;M;M;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;.;N;N;N;D
REVEL
Benign
Sift
Benign
T;T;T;.;T;T;T;D
Sift4G
Benign
T;T;T;T;T;T;.;.
Polyphen
B;B;B;B;B;.;.;.
Vest4
MutPred
Loss of glycosylation at S44 (P = 0.2272);Loss of glycosylation at S44 (P = 0.2272);Loss of glycosylation at S44 (P = 0.2272);Loss of glycosylation at S44 (P = 0.2272);Loss of glycosylation at S44 (P = 0.2272);Loss of glycosylation at S44 (P = 0.2272);Loss of glycosylation at S44 (P = 0.2272);Loss of glycosylation at S44 (P = 0.2272);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at