Genetic Variant FOXN1:c.-14-145_-14-124delTCTCTCTCTCTCTCTCTCTCTC (chr17-28523792-TTCTCTCTCTCTCTCTCTCTCTC-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001369369.1(FOXN1):c.-14-145_-14-124delTCTCTCTCTCTCTCTCTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000461 in 650,272 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. The gene FOXN1 is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.000049 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

FOXN1
NM_001369369.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.129

Publications

1 publications found

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]

FOXN1 links:

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]

RSKR links:

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ACMG classification

Specifications for FOXN1 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369369.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXN1	NM_001369369.1	MANE Select	c.-14-145_-14-124delTCTCTCTCTCTCTCTCTCTCTC		intron	N/A	NP_001356298.1	O15353
	FOXN1	NM_003593.3		c.-177_-156delTCTCTCTCTCTCTCTCTCTCTC		upstream_gene	N/A	NP_003584.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FOXN1	ENST00000579795.6	TSL:1 MANE Select	c.-14-163_-14-142delTCTCTCTCTCTCTCTCTCTCTC	intron	N/A	ENSP00000464645.1	O15353
RSKR	ENST00000481916.6	TSL:1	n.1196-67705_1196-67684delGAGAGAGAGAGAGAGAGAGAGA	intron	N/A	ENSP00000436369.2	Q96LW2-2
FOXN1	ENST00000577936.2	TSL:4	c.-9-168_-9-147delTCTCTCTCTCTCTCTCTCTCTC	intron	N/A	ENSP00000462159.2	O15353

Frequencies

GnomAD3 genomes

AF:

0.0000485

AC:

AN:

144256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000797

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000292

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000103

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000299

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000455

AC:

AN:

506016

Hom.:

AF XY:

0.0000478

AC XY:

AN XY:

272062

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

14054

American (AMR)

AF:

0.0000712

AC:

AN:

28076

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17588

East Asian (EAS)

AF:

0.00

AC:

AN:

30846

South Asian (SAS)

AF:

0.0000351

AC:

AN:

57036

European-Finnish (FIN)

AF:

0.0000563

AC:

AN:

35500

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2412

European-Non Finnish (NFE)

AF:

0.0000547

AC:

AN:

292512

Other (OTH)

AF:

0.0000357

AC:

AN:

27992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.403

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000485

AC:

AN:

144256

Hom.:

Cov.:

AF XY:

0.0000286

AC XY:

AN XY:

69838

show subpopulations

African (AFR)

AF:

0.0000797

AC:

AN:

37634

American (AMR)

AF:

0.00

AC:

AN:

14316

Ashkenazi Jewish (ASJ)

AF:

0.000292

AC:

AN:

3430

East Asian (EAS)

AF:

0.00

AC:

AN:

4780

South Asian (SAS)

AF:

0.00

AC:

AN:

4446

European-Finnish (FIN)

AF:

0.000103

AC:

AN:

9668

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000299

AC:

AN:

66804

Other (OTH)

AF:

0.00

AC:

AN:

1976

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.639

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.13

Splicing

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

Publications

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17-28523792-TTCTCTCTCTCTCTCTCTCTCTCTCTCTC-TTCTCTC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over