17-28523792-TTCTCTCTCTCTCTCTCTCTCTCTCTCTC-TTCTCTCTCTCTCTCTC

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS1

The NM_001369369.1(FOXN1):​c.-14-135_-14-124delTCTCTCTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 648,990 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 0)
Exomes 𝑓: 0.0012 ( 0 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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00129 (186/144350) while in subpopulation AFR AF= 0.00403 (152/37742). AF 95% confidence interval is 0.0035. There are 1 homozygotes in gnomad4. There are 82 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FOXN1NM_001369369.1 linkc.-14-135_-14-124delTCTCTCTCTCTC 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_-14-152delTCTCTCTCTCTC intron_variant Intron 1 of 8 1 NM_001369369.1 ENSP00000464645.1 O15353
RSKRENST00000481916.6 linkn.*1196-67695_*1196-67684delGAGAGAGAGAGA intron_variant Intron 7 of 7 1 ENSP00000436369.2 Q96LW2-2
FOXN1ENST00000577936.2 linkc.-9-168_-9-157delTCTCTCTCTCTC intron_variant Intron 1 of 8 4 ENSP00000462159.2 O15353J3KRT9

Frequencies

GnomAD3 genomes
AF:
0.00126
AC:
182
AN:
144250
Hom.:
1
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00393
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000629
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000209
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000359
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00122
AC:
615
AN:
504640
Hom.:
0
AF XY:
0.00118
AC XY:
319
AN XY:
271308
show subpopulations
Gnomad4 AFR exome
AF:
0.00675
Gnomad4 AMR exome
AF:
0.00107
Gnomad4 ASJ exome
AF:
0.00188
Gnomad4 EAS exome
AF:
0.000325
Gnomad4 SAS exome
AF:
0.000756
Gnomad4 FIN exome
AF:
0.000764
Gnomad4 NFE exome
AF:
0.00113
Gnomad4 OTH exome
AF:
0.00158
GnomAD4 genome
AF:
0.00129
AC:
186
AN:
144350
Hom.:
1
Cov.:
0
AF XY:
0.00117
AC XY:
82
AN XY:
69948
show subpopulations
Gnomad4 AFR
AF:
0.00403
Gnomad4 AMR
AF:
0.000628
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000210
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000359
Gnomad4 OTH
AF:
0.00

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