17-28523792-TTCTCTCTCTCTCTCTCTCTCTCTCTCTC-TTCTCTCTCTCTCTCTCTCTCTCTCTCTCTC

Variant names:

• chr17-28523792-T-TTC
• rs10527420
• NM_001369369.1:c.-14-125_-14-124dupTC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001369369.1(FOXN1):​c.-14-125_-14-124dupTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 647,678 control chromosomes in the GnomAD database, including 36 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.014 (35 hom., cov: 0)
  • Exomes 𝑓: 0.0095 (1 hom.)
• Consequence: FOXN1 NM_001369369.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970

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

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.014 (2023/144218) while in subpopulation AFR AF= 0.0325 (1225/37658). AF 95% confidence interval is 0.031. There are 35 homozygotes in gnomad4. There are 983 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 35 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXN1	NM_001369369.1	c.-14-125_-14-124dupTC		intron_variant	Intron 1 of 8	ENST00000579795.6	NP_001356298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXN1	ENST00000579795.6	c.-14-164_-14-163insTC		intron_variant	Intron 1 of 8	1	NM_001369369.1	ENSP00000464645.1
RSKR	ENST00000481916.6	n.*1196-67684_*1196-67683insGA		intron_variant	Intron 7 of 7	1		ENSP00000436369.2
FOXN1	ENST00000577936.2	c.-9-169_-9-168insTC		intron_variant	Intron 1 of 8	4		ENSP00000462159.2
FOXN1	ENST00000226247.2	c.-178_-177insTC		upstream_gene_variant		1		ENSP00000226247.2

Frequencies

GnomAD3 genomes AF: 0.0139 AC: 2010 AN: 144122 Hom.: 34 Cov.: 0

Gnomad AFR AF: 0.0323

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00643

Gnomad ASJ AF: 0.00117

Gnomad EAS AF: 0.0124

Gnomad SAS AF: 0.0289

Gnomad FIN AF: 0.00342

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.00668

Gnomad OTH AF: 0.0162

GnomAD4 exome AF: 0.00950 AC: 4784 AN: 503460 Hom.: 1 AF XY: 0.00999 AC XY: 2704 AN XY: 270666

Gnomad4 AFR exome AF: 0.0251

Gnomad4 AMR exome AF: 0.0185

Gnomad4 ASJ exome AF: 0.00114

Gnomad4 EAS exome AF: 0.0141

Gnomad4 SAS exome AF: 0.0210

Gnomad4 FIN exome AF: 0.00495

Gnomad4 NFE exome AF: 0.00630

Gnomad4 OTH exome AF: 0.00926

GnomAD4 genome AF: 0.0140 AC: 2023 AN: 144218 Hom.: 35 Cov.: 0 AF XY: 0.0141 AC XY: 983 AN XY: 69874

Gnomad4 AFR AF: 0.0325

Gnomad4 AMR AF: 0.00642

Gnomad4 ASJ AF: 0.00117

Gnomad4 EAS AF: 0.0124

Gnomad4 SAS AF: 0.0282

Gnomad4 FIN AF: 0.00342

Gnomad4 NFE AF: 0.00668

Gnomad4 OTH AF: 0.0185

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10527420; hg19: chr17-26850810;