chr17-28524005-G-A
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001369369.1(FOXN1):c.36G>A(p.Thr12=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,612,818 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
FOXN1
NM_001369369.1 synonymous
NM_001369369.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.98
Genes affected
FOXN1 (HGNC:12765): (forkhead box N1) Mutations in the winged-helix transcription factor gene at the nude locus in mice and rats produce the pleiotropic phenotype of hairlessness and athymia, resulting in a severely compromised immune system. This gene is orthologous to the mouse and rat genes and encodes a similar DNA-binding transcription factor that is thought to regulate keratin gene expression. A mutation in this gene has been correlated with T-cell immunodeficiency, the skin disorder congenital alopecia, and nail dystrophy. Alternative splicing in the 5' UTR of this gene has been observed. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 17-28524005-G-A is Benign according to our data. Variant chr17-28524005-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2996611.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-2.98 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXN1 | NM_001369369.1 | c.36G>A | p.Thr12= | synonymous_variant | 2/9 | ENST00000579795.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXN1 | ENST00000579795.6 | c.36G>A | p.Thr12= | synonymous_variant | 2/9 | 1 | NM_001369369.1 | P1 | |
FOXN1 | ENST00000226247.2 | c.36G>A | p.Thr12= | synonymous_variant | 1/8 | 1 | P1 | ||
RSKR | ENST00000481916.6 | c.*1196-67896C>T | intron_variant, NMD_transcript_variant | 1 | |||||
FOXN1 | ENST00000577936.2 | c.36G>A | p.Thr12= | synonymous_variant | 2/9 | 4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152102Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248564Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135104
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GnomAD4 exome AF: 0.00000548 AC: 8AN: 1460716Hom.: 0 Cov.: 35 AF XY: 0.00000550 AC XY: 4AN XY: 726700
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152102Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74294
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
T-cell immunodeficiency, congenital alopecia, and nail dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 24, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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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