Genetic Variant FOXN1:c.-14-143_-14-124delTCTCTCTCTCTCTCTCTCTC (chr17-28523792-TTCTCTCTCTCTCTCTCTCTC-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_001369369.1(FOXN1):c.-14-143_-14-124delTCTCTCTCTCTCTCTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000667 in 641,554 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 0.000069 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00084 ( 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:

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 nfe. gnomad4_exome allele frequency = 0.000841 (418/497220) while in subpopulation NFE AF= 0.000931 (267/286862). AF 95% confidence interval is 0.000839. There are 0 homozygotes in gnomad4_exome. There are 245 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXN1	NM_001369369.1 link	c.-14-143_-14-124delTCTCTCTCTCTCTCTCTCTC		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_-14-144delTCTCTCTCTCTCTCTCTCTC	intron_variant	Intron 1 of 8	1	NM_001369369.1	ENSP00000464645.1	O15353
RSKR	ENST00000481916.6 link	n.1196-67703_1196-67684delGAGAGAGAGAGAGAGAGAGA	intron_variant	Intron 7 of 7	1		ENSP00000436369.2	Q96LW2-2
FOXN1	ENST00000577936.2 link	c.-9-168_-9-149delTCTCTCTCTCTCTCTCTCTC	intron_variant	Intron 1 of 8	4		ENSP00000462159.2	O15353J3KRT9
FOXN1	ENST00000226247.2 link	c.-177_-158delTCTCTCTCTCTCTCTCTCTC	upstream_gene_variant		1		ENSP00000226247.2	O15353

Frequencies

GnomAD3 genomes

AF:

0.0000693

AC:

AN:

144234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000797

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000105

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000841

AC:

418

AN:

497220

Hom.:

AF XY:

0.000916

AC XY:

245

AN XY:

267386

show subpopulations

Gnomad4 AFR exome

AF:

0.000573

Gnomad4 AMR exome

AF:

0.000646

Gnomad4 ASJ exome

AF:

0.000869

Gnomad4 EAS exome

AF:

0.000429

Gnomad4 SAS exome

AF:

0.000747

Gnomad4 FIN exome

AF:

0.00115

Gnomad4 NFE exome

AF:

0.000931

Gnomad4 OTH exome

AF:

0.000473

GnomAD4 genome

AF:

0.0000693

AC:

AN:

144334

Hom.:

Cov.:

AF XY:

0.0000429

AC XY:

AN XY:

69938

show subpopulations

Gnomad4 AFR

AF:

0.0000795

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000105

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-TTCTCTCTC

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