17-28523792-TTCTCTCTCTCTCTCTCTCTCTCTCTCTC-TTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTC

Variant summary

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

The NM_001369369.1(FOXN1):​c.-14-137_-14-124dupTCTCTCTCTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000363 in 650,380 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00087 ( 0 hom., cov: 0)
Exomes 𝑓: 0.00022 ( 0 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 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 = 0.000873 (126/144328) while in subpopulation AFR AF= 0.00225 (85/37732). AF 95% confidence interval is 0.00187. There are 0 homozygotes in gnomad4. There are 60 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.-14-137_-14-124dupTCTCTCTCTCTCTC 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_-14-163insTCTCTCTCTCTCTC intron_variant Intron 1 of 8 1 NM_001369369.1 ENSP00000464645.1 O15353
RSKRENST00000481916.6 linkn.*1196-67684_*1196-67683insGAGAGAGAGAGAGA intron_variant Intron 7 of 7 1 ENSP00000436369.2 Q96LW2-2
FOXN1ENST00000577936.2 linkc.-9-169_-9-168insTCTCTCTCTCTCTC intron_variant Intron 1 of 8 4 ENSP00000462159.2 O15353J3KRT9

Frequencies

GnomAD3 genomes
AF:
0.000881
AC:
127
AN:
144228
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00226
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000978
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000838
Gnomad SAS
AF:
0.000675
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0129
Gnomad NFE
AF:
0.000254
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.000217
AC:
110
AN:
506052
Hom.:
0
AF XY:
0.000239
AC XY:
65
AN XY:
272078
show subpopulations
Gnomad4 AFR exome
AF:
0.00171
Gnomad4 AMR exome
AF:
0.000214
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000195
Gnomad4 SAS exome
AF:
0.000508
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000133
Gnomad4 OTH exome
AF:
0.000214
GnomAD4 genome
AF:
0.000873
AC:
126
AN:
144328
Hom.:
0
Cov.:
0
AF XY:
0.000858
AC XY:
60
AN XY:
69934
show subpopulations
Gnomad4 AFR
AF:
0.00225
Gnomad4 AMR
AF:
0.000977
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000840
Gnomad4 SAS
AF:
0.000676
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000255
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