17-28523792-TTCTCTCTCTCTCTCTCTCTCTCTCTCTC-TTCTCTCTCTCTCTCTCTCTCTCTC

Variant summary

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

The NM_001369369.1(FOXN1):​c.-14-127_-14-124delTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00377 in 649,812 control chromosomes in the GnomAD database, including 9 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0049 ( 6 hom., cov: 0)
Exomes 𝑓: 0.0035 ( 3 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 = 0.0049 (707/144330) while in subpopulation AFR AF= 0.00917 (346/37732). AF 95% confidence interval is 0.00837. There are 6 homozygotes in gnomad4. There are 326 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 6 SD gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FOXN1NM_001369369.1 linkc.-14-127_-14-124delTCTC 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_-14-160delTCTC intron_variant Intron 1 of 8 1 NM_001369369.1 ENSP00000464645.1 O15353
RSKRENST00000481916.6 linkn.*1196-67687_*1196-67684delGAGA intron_variant Intron 7 of 7 1 ENSP00000436369.2 Q96LW2-2
FOXN1ENST00000577936.2 linkc.-9-168_-9-165delTCTC intron_variant Intron 1 of 8 4 ENSP00000462159.2 O15353J3KRT9

Frequencies

GnomAD3 genomes
AF:
0.00490
AC:
707
AN:
144230
Hom.:
6
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00920
Gnomad AMI
AF:
0.00562
Gnomad AMR
AF:
0.00510
Gnomad ASJ
AF:
0.00701
Gnomad EAS
AF:
0.000418
Gnomad SAS
AF:
0.00450
Gnomad FIN
AF:
0.000103
Gnomad MID
AF:
0.0288
Gnomad NFE
AF:
0.00314
Gnomad OTH
AF:
0.00860
GnomAD4 exome
AF:
0.00345
AC:
1745
AN:
505482
Hom.:
3
AF XY:
0.00357
AC XY:
971
AN XY:
271784
show subpopulations
Gnomad4 AFR exome
AF:
0.0153
Gnomad4 AMR exome
AF:
0.00282
Gnomad4 ASJ exome
AF:
0.00432
Gnomad4 EAS exome
AF:
0.000292
Gnomad4 SAS exome
AF:
0.00424
Gnomad4 FIN exome
AF:
0.000394
Gnomad4 NFE exome
AF:
0.00314
Gnomad4 OTH exome
AF:
0.00576
GnomAD4 genome
AF:
0.00490
AC:
707
AN:
144330
Hom.:
6
Cov.:
0
AF XY:
0.00466
AC XY:
326
AN XY:
69934
show subpopulations
Gnomad4 AFR
AF:
0.00917
Gnomad4 AMR
AF:
0.00509
Gnomad4 ASJ
AF:
0.00701
Gnomad4 EAS
AF:
0.000419
Gnomad4 SAS
AF:
0.00450
Gnomad4 FIN
AF:
0.000103
Gnomad4 NFE
AF:
0.00314
Gnomad4 OTH
AF:
0.00902

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

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