17-28523792-TTCTCTCTCTCTCTCTCTCTCTCTCTCTC-TTCTCTCTCTCTCTCTCTCTCTCTCTCTCTC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_001369369.1(FOXN1):​c.-14-125_-14-124dupTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 647,678 control chromosomes in the GnomAD database, including 36 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.014 ( 35 hom., cov: 0)
Exomes 𝑓: 0.0095 ( 1 hom. )

Consequence

FOXN1
NM_001369369.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0970
Variant links:
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]
RSKR (HGNC:26314): (ribosomal protein S6 kinase related) Predicted to enable protein kinase activity. Predicted to be involved in protein phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.014 (2023/144218) while in subpopulation AFR AF= 0.0325 (1225/37658). AF 95% confidence interval is 0.031. There are 35 homozygotes in gnomad4. There are 983 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 35 SD gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FOXN1NM_001369369.1 linkc.-14-125_-14-124dupTC intron_variant Intron 1 of 8 ENST00000579795.6 NP_001356298.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FOXN1ENST00000579795.6 linkc.-14-164_-14-163insTC intron_variant Intron 1 of 8 1 NM_001369369.1 ENSP00000464645.1 O15353
RSKRENST00000481916.6 linkn.*1196-67684_*1196-67683insGA intron_variant Intron 7 of 7 1 ENSP00000436369.2 Q96LW2-2
FOXN1ENST00000577936.2 linkc.-9-169_-9-168insTC intron_variant Intron 1 of 8 4 ENSP00000462159.2 O15353J3KRT9

Frequencies

GnomAD3 genomes
AF:
0.0139
AC:
2010
AN:
144122
Hom.:
34
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0323
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00643
Gnomad ASJ
AF:
0.00117
Gnomad EAS
AF:
0.0124
Gnomad SAS
AF:
0.0289
Gnomad FIN
AF:
0.00342
Gnomad MID
AF:
0.00641
Gnomad NFE
AF:
0.00668
Gnomad OTH
AF:
0.0162
GnomAD4 exome
AF:
0.00950
AC:
4784
AN:
503460
Hom.:
1
AF XY:
0.00999
AC XY:
2704
AN XY:
270666
show subpopulations
Gnomad4 AFR exome
AF:
0.0251
Gnomad4 AMR exome
AF:
0.0185
Gnomad4 ASJ exome
AF:
0.00114
Gnomad4 EAS exome
AF:
0.0141
Gnomad4 SAS exome
AF:
0.0210
Gnomad4 FIN exome
AF:
0.00495
Gnomad4 NFE exome
AF:
0.00630
Gnomad4 OTH exome
AF:
0.00926
GnomAD4 genome
AF:
0.0140
AC:
2023
AN:
144218
Hom.:
35
Cov.:
0
AF XY:
0.0141
AC XY:
983
AN XY:
69874
show subpopulations
Gnomad4 AFR
AF:
0.0325
Gnomad4 AMR
AF:
0.00642
Gnomad4 ASJ
AF:
0.00117
Gnomad4 EAS
AF:
0.0124
Gnomad4 SAS
AF:
0.0282
Gnomad4 FIN
AF:
0.00342
Gnomad4 NFE
AF:
0.00668
Gnomad4 OTH
AF:
0.0185

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10527420; hg19: chr17-26850810; API