chr14-89412353-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_005197.4(FOXN3):c.124G>A(p.Asp42Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,614,148 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: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000019 ( 0 hom. )
Consequence
FOXN3
NM_005197.4 missense
NM_005197.4 missense
Scores
5
13
Clinical Significance
Conservation
PhyloP100: 3.93
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.069618315).
BS2
?
High AC in GnomAdExome at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXN3 | NM_005197.4 | c.124G>A | p.Asp42Asn | missense_variant | 2/6 | ENST00000557258.6 | |
FOXN3 | NM_001085471.2 | c.124G>A | p.Asp42Asn | missense_variant | 2/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXN3 | ENST00000557258.6 | c.124G>A | p.Asp42Asn | missense_variant | 2/6 | 1 | NM_005197.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152144Hom.: 0 Cov.: 31
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251378Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135884
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GnomAD4 exome AF: 0.0000192 AC: 28AN: 1461886Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13AN XY: 727242
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152262Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74444
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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 | Sep 12, 2023 | The c.124G>A (p.D42N) alteration is located in exon 2 (coding exon 1) of the FOXN3 gene. This alteration results from a G to A substitution at nucleotide position 124, causing the aspartic acid (D) at amino acid position 42 to be replaced by an asparagine (N). 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
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T;.;.;.;T;T;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L;L;L;L;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
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
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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