17-28523792-TTCTCTCTCTCTCTCTCTCTCTCTCTCTC-TTCTCTCTCTC

Variant names:

• chr17-28523792-TTCTCTCTCTCTCTCTCTC-T
• rs10527420
• NM_001369369.1:c.-14-141_-14-124delTCTCTCTCTCTCTCTCTC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001369369.1(FOXN1):​c.-14-141_-14-124delTCTCTCTCTCTCTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0468 in 568,938 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 0.00053 (1 hom., cov: 0)
  • Exomes 𝑓: 0.062 (35 hom.)
• Consequence: FOXN1 NM_001369369.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129

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.

• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXN1	NM_001369369.1	c.-14-141_-14-124delTCTCTCTCTCTCTCTCTC		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.-14-163_-14-146delTCTCTCTCTCTCTCTCTC		intron_variant	Intron 1 of 8	1	NM_001369369.1	ENSP00000464645.1
RSKR	ENST00000481916.6	n.*1196-67701_*1196-67684delGAGAGAGAGAGAGAGAGA		intron_variant	Intron 7 of 7	1		ENSP00000436369.2
FOXN1	ENST00000577936.2	c.-9-168_-9-151delTCTCTCTCTCTCTCTCTC		intron_variant	Intron 1 of 8	4		ENSP00000462159.2
FOXN1	ENST00000226247.2	c.-177_-160delTCTCTCTCTCTCTCTCTC		upstream_gene_variant		1		ENSP00000226247.2

Frequencies

GnomAD3 genomes AF: 0.000535 AC: 77 AN: 143848 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000210

Gnomad ASJ AF: 0.000292

Gnomad EAS AF: 0.000209

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000631

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000300

Gnomad OTH AF: 0.000508

GnomAD4 exome AF: 0.0624 AC: 26534 AN: 424994 Hom.: 35 AF XY: 0.0628 AC XY: 14367 AN XY: 228936

Gnomad4 AFR exome AF: 0.0201

Gnomad4 AMR exome AF: 0.0420

Gnomad4 ASJ exome AF: 0.0679

Gnomad4 EAS exome AF: 0.0583

Gnomad4 SAS exome AF: 0.0523

Gnomad4 FIN exome AF: 0.0602

Gnomad4 NFE exome AF: 0.0698

Gnomad4 OTH exome AF: 0.0594

GnomAD4 genome AF: 0.000535 AC: 77 AN: 143944 Hom.: 1 Cov.: 0 AF XY: 0.000517 AC XY: 36 AN XY: 69688

Gnomad4 AFR AF: 0.00119

Gnomad4 AMR AF: 0.000210

Gnomad4 ASJ AF: 0.000292

Gnomad4 EAS AF: 0.000210

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000631

Gnomad4 NFE AF: 0.000300

Gnomad4 OTH AF: 0.000503

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;