17-28523792-TTCTCTCTCTCTCTCTCTCTCTCTCTCTC-TTCTCTCTCTCTCTC

Variant summary

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

The NM_001369369.1(FOXN1):​c.-14-137_-14-124delTCTCTCTCTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00216 in 649,958 control chromosomes in the GnomAD database, including 11 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 0)
Exomes 𝑓: 0.0022 ( 11 hom. )

Consequence

FOXN1
NM_001369369.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.129
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00188 (272/144356) while in subpopulation SAS AF= 0.00811 (36/4440). AF 95% confidence interval is 0.00602. There are 0 homozygotes in gnomad4. There are 143 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 11 SD gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FOXN1NM_001369369.1 linkc.-14-137_-14-124delTCTCTCTCTCTCTC 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.-14-163_-14-150delTCTCTCTCTCTCTC intron_variant Intron 1 of 8 1 NM_001369369.1 ENSP00000464645.1 O15353
RSKRENST00000481916.6 linkn.*1196-67697_*1196-67684delGAGAGAGAGAGAGA intron_variant Intron 7 of 7 1 ENSP00000436369.2 Q96LW2-2
FOXN1ENST00000577936.2 linkc.-9-168_-9-155delTCTCTCTCTCTCTC intron_variant Intron 1 of 8 4 ENSP00000462159.2 O15353J3KRT9

Frequencies

GnomAD3 genomes
AF:
0.00189
AC:
272
AN:
144256
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00279
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00384
Gnomad ASJ
AF:
0.00204
Gnomad EAS
AF:
0.00230
Gnomad SAS
AF:
0.00832
Gnomad FIN
AF:
0.000207
Gnomad MID
AF:
0.00641
Gnomad NFE
AF:
0.000763
Gnomad OTH
AF:
0.00101
GnomAD4 exome
AF:
0.00224
AC:
1131
AN:
505602
Hom.:
11
AF XY:
0.00268
AC XY:
729
AN XY:
271846
show subpopulations
Gnomad4 AFR exome
AF:
0.00256
Gnomad4 AMR exome
AF:
0.00506
Gnomad4 ASJ exome
AF:
0.00404
Gnomad4 EAS exome
AF:
0.00120
Gnomad4 SAS exome
AF:
0.00888
Gnomad4 FIN exome
AF:
0.000592
Gnomad4 NFE exome
AF:
0.000852
Gnomad4 OTH exome
AF:
0.00204
GnomAD4 genome
AF:
0.00188
AC:
272
AN:
144356
Hom.:
0
Cov.:
0
AF XY:
0.00204
AC XY:
143
AN XY:
69950
show subpopulations
Gnomad4 AFR
AF:
0.00278
Gnomad4 AMR
AF:
0.00391
Gnomad4 ASJ
AF:
0.00204
Gnomad4 EAS
AF:
0.00231
Gnomad4 SAS
AF:
0.00811
Gnomad4 FIN
AF:
0.000207
Gnomad4 NFE
AF:
0.000763
Gnomad4 OTH
AF:
0.00100

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