17-28523792-TTCTCTCTCTCTCTCTCTCTCTCTCTCTC-TTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTC

Variant names:

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

Variant summary

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

The NM_001369369.1(FOXN1):​c.-14-135_-14-124dupTCTCTCTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 650,180 control chromosomes in the GnomAD database, including 5 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0033 (4 hom., cov: 0)
  • Exomes 𝑓: 0.00088 (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 = 0.00332 (479/144284) while in subpopulation AFR AF= 0.00843 (318/37702). AF 95% confidence interval is 0.00767. There are 4 homozygotes in gnomad4. There are 236 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXN1	NM_001369369.1	c.-14-135_-14-124dupTCTCTCTCTCTC		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_-14-163insTCTCTCTCTCTC		intron_variant	Intron 1 of 8	1	NM_001369369.1	ENSP00000464645.1
RSKR	ENST00000481916.6	n.*1196-67684_*1196-67683insGAGAGAGAGAGA		intron_variant	Intron 7 of 7	1		ENSP00000436369.2
FOXN1	ENST00000577936.2	c.-9-169_-9-168insTCTCTCTCTCTC		intron_variant	Intron 1 of 8	4		ENSP00000462159.2

Frequencies

GnomAD3 genomes AF: 0.00332 AC: 478 AN: 144186 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.00838

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00217

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000628

Gnomad SAS AF: 0.00293

Gnomad FIN AF: 0.00135

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.00150

Gnomad OTH AF: 0.00101

GnomAD4 exome AF: 0.000882 AC: 446 AN: 505896 Hom.: 1 AF XY: 0.000908 AC XY: 247 AN XY: 272026

Gnomad4 AFR exome AF: 0.00507

Gnomad4 AMR exome AF: 0.000713

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000713

Gnomad4 SAS exome AF: 0.00144

Gnomad4 FIN exome AF: 0.00121

Gnomad4 NFE exome AF: 0.000612

Gnomad4 OTH exome AF: 0.000965

GnomAD4 genome AF: 0.00332 AC: 479 AN: 144284 Hom.: 4 Cov.: 0 AF XY: 0.00338 AC XY: 236 AN XY: 69918

Gnomad4 AFR AF: 0.00843

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000629

Gnomad4 SAS AF: 0.00270

Gnomad4 FIN AF: 0.00135

Gnomad4 NFE AF: 0.00150

Gnomad4 OTH AF: 0.00100

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;