17-28523792-TTCTCTCTCTCTCTCTCTCTCTCTCTCTC-TTCTCTCTCTCTCTCTCTCTCTC

Variant names:

• chr17-28523792-TTCTCTC-T
• rs10527420
• NM_001369369.1:c.-14-129_-14-124delTCTCTC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001369369.1(FOXN1):​c.-14-129_-14-124delTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00768 in 649,976 control chromosomes in the GnomAD database, including 14 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.011 (11 hom., cov: 0)
  • Exomes 𝑓: 0.0067 (3 hom.)
• Consequence: FOXN1 NM_001369369.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.011 (1592/144326) while in subpopulation AFR AF = 0.0187 (707/37726). AF 95% confidence interval is 0.0176. There are 11 homozygotes in GnomAd4. There are 743 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AD,AR,SD gene

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.-14-129_-14-124delTCTCTC		intron	N/A	NP_001356298.1	O15353
	FOXN1	NM_003593.3		c.-177_-172delTCTCTC		upstream_gene	N/A	NP_003584.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXN1	ENST00000579795.6	TSL:1 MANE Select	c.-14-163_-14-158delTCTCTC		intron	N/A	ENSP00000464645.1	O15353
	RSKR	ENST00000481916.6	TSL:1	n.*1196-67689_*1196-67684delGAGAGA		intron	N/A	ENSP00000436369.2	Q96LW2-2
	FOXN1	ENST00000577936.2	TSL:4	c.-9-168_-9-163delTCTCTC		intron	N/A	ENSP00000462159.2	O15353

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1586 AN: 144226 Hom.: 11 Cov.: 0

Gnomad AFR AF: 0.0187

Gnomad AMI AF: 0.0652

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.00408

Gnomad EAS AF: 0.00105

Gnomad SAS AF: 0.00315

Gnomad FIN AF: 0.00176

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.00846

Gnomad OTH AF: 0.0111

GnomAD4 exome AF: 0.00672 AC: 3399 AN: 505650 Hom.: 3 AF XY: 0.00638 AC XY: 1734 AN XY: 271876

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0188 AC: 263 AN: 14010

American (AMR) AF: 0.00930 AC: 261 AN: 28064

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 66 AN: 17582

East Asian (EAS) AF: 0.00233 AC: 72 AN: 30848

South Asian (SAS) AF: 0.00349 AC: 199 AN: 56982

European-Finnish (FIN) AF: 0.00203 AC: 72 AN: 35492

Middle Eastern (MID) AF: 0.00873 AC: 21 AN: 2406

European-Non Finnish (NFE) AF: 0.00753 AC: 2200 AN: 292292

Other (OTH) AF: 0.00876 AC: 245 AN: 27974

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0110 AC: 1592 AN: 144326 Hom.: 11 Cov.: 0 AF XY: 0.0106 AC XY: 743 AN XY: 69930

African (AFR) AF: 0.0187 AC: 707 AN: 37726

American (AMR) AF: 0.0130 AC: 186 AN: 14334

Ashkenazi Jewish (ASJ) AF: 0.00408 AC: 14 AN: 3430

East Asian (EAS) AF: 0.00105 AC: 5 AN: 4768

South Asian (SAS) AF: 0.00315 AC: 14 AN: 4440

European-Finnish (FIN) AF: 0.00176 AC: 17 AN: 9666

Middle Eastern (MID) AF: 0.00690 AC: 2 AN: 290

European-Non Finnish (NFE) AF: 0.00846 AC: 565 AN: 66786

Other (OTH) AF: 0.0120 AC: 24 AN: 1996

Alfa AF: 0.00403 Hom.: 106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs10527420; hg19: chr17-26850810;