Genetic Variant FOXN1:c.-14-145_-14-124delTCTCTCTCTCTCTCTCTCTCTC (chr17-28523792-TTCTCTCTCTCTCTCTCTCTCTC-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

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

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXN1	NM_001369369.1 link	c.-14-145_-14-124delTCTCTCTCTCTCTCTCTCTCTC		intron_variant	Intron 1 of 8	ENST00000579795.6	NP_001356298.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FOXN1	ENST00000579795.6 link	c.-14-163_-14-142delTCTCTCTCTCTCTCTCTCTCTC	intron_variant	Intron 1 of 8	1	NM_001369369.1	ENSP00000464645.1	O15353
RSKR	ENST00000481916.6 link	n.1196-67705_1196-67684delGAGAGAGAGAGAGAGAGAGAGA	intron_variant	Intron 7 of 7	1		ENSP00000436369.2	Q96LW2-2
FOXN1	ENST00000577936.2 link	c.-9-168_-9-147delTCTCTCTCTCTCTCTCTCTCTC	intron_variant	Intron 1 of 8	4		ENSP00000462159.2	O15353J3KRT9
FOXN1	ENST00000226247.2 link	c.-177_-156delTCTCTCTCTCTCTCTCTCTCTC	upstream_gene_variant		1		ENSP00000226247.2	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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000712

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000351

Gnomad4 FIN exome

AF:

0.0000563

Gnomad4 NFE exome

AF:

0.0000547

Gnomad4 OTH exome

AF:

0.0000357

GnomAD4 genome

AF:

0.0000485

AC:

AN:

144256

Hom.:

Cov.:

AF XY:

0.0000286

AC XY:

AN XY:

69838

show subpopulations

Gnomad4 AFR

AF:

0.0000797

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000292

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000103

Gnomad4 NFE

AF:

0.0000299

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.

17-28523792-TTCTCTCTCTCTCTCTCTCTCTCTCTCTC-TTCTCTC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over