rs779728088
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001369369.1(FOXN1):c.79C>T(p.Leu27Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,120 control chromosomes in the GnomAD database, with no homozygous occurrence. 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
Consequence
NM_001369369.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FOXN1 | NM_001369369.1 | c.79C>T | p.Leu27Phe | missense_variant | Exon 2 of 9 | ENST00000579795.6 | NP_001356298.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FOXN1 | ENST00000579795.6 | c.79C>T | p.Leu27Phe | missense_variant | Exon 2 of 9 | 1 | NM_001369369.1 | ENSP00000464645.1 | ||
FOXN1 | ENST00000226247.2 | c.79C>T | p.Leu27Phe | missense_variant | Exon 1 of 8 | 1 | ENSP00000226247.2 | |||
RSKR | ENST00000481916.6 | n.*1196-67939G>A | intron_variant | Intron 7 of 7 | 1 | ENSP00000436369.2 | ||||
FOXN1 | ENST00000577936.2 | c.79C>T | p.Leu27Phe | missense_variant | Exon 2 of 9 | 4 | ENSP00000462159.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000816 AC: 2AN: 244976Hom.: 0 AF XY: 0.00000749 AC XY: 1AN XY: 133582
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459120Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1AN XY: 725920
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
T-cell immunodeficiency, congenital alopecia, and nail dystrophy Uncertain:1
This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 27 of the FOXN1 protein (p.Leu27Phe). This variant is present in population databases (rs779728088, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with FOXN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 468553). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The phenylalanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at