17-28523792-TTCTCTCTCTCTCTCTCTCTCTCTCTCTC-TTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTC

Variant names:

• chr17-28523792-T-TTCTCTCTC
• rs10527420
• NM_001369369.1:c.-14-131_-14-124dupTCTCTCTC

Variant summary

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

The NM_001369369.1(FOXN1):​c.-14-131_-14-124dupTCTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00506 in 649,048 control chromosomes in the GnomAD database, including 17 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0079 (11 hom., cov: 0)
  • Exomes 𝑓: 0.0043 (6 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 eas. gnomad4 allele frequency = 0.00786 (1133/144224) while in subpopulation EAS AF= 0.0164 (78/4760). AF 95% confidence interval is 0.0137. There are 11 homozygotes in gnomad4. There are 530 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 11 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXN1	NM_001369369.1	c.-14-131_-14-124dupTCTCTCTC		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_-14-163insTCTCTCTC		intron_variant	Intron 1 of 8	1	NM_001369369.1	ENSP00000464645.1
RSKR	ENST00000481916.6	n.*1196-67684_*1196-67683insGAGAGAGA		intron_variant	Intron 7 of 7	1		ENSP00000436369.2
FOXN1	ENST00000577936.2	c.-9-169_-9-168insTCTCTCTC		intron_variant	Intron 1 of 8	4		ENSP00000462159.2

Frequencies

GnomAD3 genomes AF: 0.00789 AC: 1137 AN: 144124 Hom.: 11 Cov.: 0

Gnomad AFR AF: 0.0147

Gnomad AMI AF: 0.0113

Gnomad AMR AF: 0.00685

Gnomad ASJ AF: 0.00904

Gnomad EAS AF: 0.0166

Gnomad SAS AF: 0.00428

Gnomad FIN AF: 0.00259

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00470

Gnomad OTH AF: 0.00457

GnomAD4 exome AF: 0.00426 AC: 2149 AN: 504824 Hom.: 6 AF XY: 0.00401 AC XY: 1088 AN XY: 271472

Gnomad4 AFR exome AF: 0.0105

Gnomad4 AMR exome AF: 0.00754

Gnomad4 ASJ exome AF: 0.00394

Gnomad4 EAS exome AF: 0.0101

Gnomad4 SAS exome AF: 0.00346

Gnomad4 FIN exome AF: 0.00401

Gnomad4 NFE exome AF: 0.00314

Gnomad4 OTH exome AF: 0.00537

GnomAD4 genome AF: 0.00786 AC: 1133 AN: 144224 Hom.: 11 Cov.: 0 AF XY: 0.00758 AC XY: 530 AN XY: 69886

Gnomad4 AFR AF: 0.0147

Gnomad4 AMR AF: 0.00670

Gnomad4 ASJ AF: 0.00904

Gnomad4 EAS AF: 0.0164

Gnomad4 SAS AF: 0.00383

Gnomad4 FIN AF: 0.00259

Gnomad4 NFE AF: 0.00470

Gnomad4 OTH AF: 0.00452

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;