17-28523792-TTCTCTCTCTCTCTCTCTCTCTCTCTCTC-TTCTCTCTCTCTCTCTC

Variant names:

• chr17-28523792-TTCTCTCTCTCTC-T
• rs10527420
• NM_001369369.1:c.-14-135_-14-124delTCTCTCTCTCTC

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001369369.1(FOXN1):​c.-14-135_-14-124delTCTCTCTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 648,990 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0012 (0 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 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 afr. gnomad4 allele frequency = 0.00129 (186/144350) while in subpopulation AFR AF= 0.00403 (152/37742). AF 95% confidence interval is 0.0035. There are 1 homozygotes in gnomad4. There are 82 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXN1	NM_001369369.1	c.-14-135_-14-124delTCTCTCTCTCTC		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_-14-152delTCTCTCTCTCTC		intron_variant	Intron 1 of 8	1	NM_001369369.1	ENSP00000464645.1
RSKR	ENST00000481916.6	n.*1196-67695_*1196-67684delGAGAGAGAGAGA		intron_variant	Intron 7 of 7	1		ENSP00000436369.2
FOXN1	ENST00000577936.2	c.-9-168_-9-157delTCTCTCTCTCTC		intron_variant	Intron 1 of 8	4		ENSP00000462159.2
FOXN1	ENST00000226247.2	c.-177_-166delTCTCTCTCTCTC		upstream_gene_variant		1		ENSP00000226247.2

Frequencies

GnomAD3 genomes AF: 0.00126 AC: 182 AN: 144250 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00393

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000629

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000209

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000359

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00122 AC: 615 AN: 504640 Hom.: 0 AF XY: 0.00118 AC XY: 319 AN XY: 271308

Gnomad4 AFR exome AF: 0.00675

Gnomad4 AMR exome AF: 0.00107

Gnomad4 ASJ exome AF: 0.00188

Gnomad4 EAS exome AF: 0.000325

Gnomad4 SAS exome AF: 0.000756

Gnomad4 FIN exome AF: 0.000764

Gnomad4 NFE exome AF: 0.00113

Gnomad4 OTH exome AF: 0.00158

GnomAD4 genome AF: 0.00129 AC: 186 AN: 144350 Hom.: 1 Cov.: 0 AF XY: 0.00117 AC XY: 82 AN XY: 69948

Gnomad4 AFR AF: 0.00403

Gnomad4 AMR AF: 0.000628

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000210

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000359

Gnomad4 OTH AF: 0.00

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;