17-28523792-TTCTCTCTCTCTCTCTCTCTCTCTCTCTC-TTCTCTCTCTCTCTCTCTCTCTCTC

Variant names:

• chr17-28523792-TTCTC-T
• rs10527420
• NM_001369369.1:c.-14-127_-14-124delTCTC

Variant summary

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

The NM_001369369.1(FOXN1):​c.-14-127_-14-124delTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00377 in 649,812 control chromosomes in the GnomAD database, including 9 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0049 (6 hom., cov: 0)
  • Exomes 𝑓: 0.0035 (3 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 = 0.0049 (707/144330) while in subpopulation AFR AF= 0.00917 (346/37732). AF 95% confidence interval is 0.00837. There are 6 homozygotes in gnomad4. There are 326 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXN1	NM_001369369.1	c.-14-127_-14-124delTCTC		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_-14-160delTCTC		intron_variant	Intron 1 of 8	1	NM_001369369.1	ENSP00000464645.1
RSKR	ENST00000481916.6	n.*1196-67687_*1196-67684delGAGA		intron_variant	Intron 7 of 7	1		ENSP00000436369.2
FOXN1	ENST00000577936.2	c.-9-168_-9-165delTCTC		intron_variant	Intron 1 of 8	4		ENSP00000462159.2
FOXN1	ENST00000226247.2	c.-177_-174delTCTC		upstream_gene_variant		1		ENSP00000226247.2

Frequencies

GnomAD3 genomes AF: 0.00490 AC: 707 AN: 144230 Hom.: 6 Cov.: 0

Gnomad AFR AF: 0.00920

Gnomad AMI AF: 0.00562

Gnomad AMR AF: 0.00510

Gnomad ASJ AF: 0.00701

Gnomad EAS AF: 0.000418

Gnomad SAS AF: 0.00450

Gnomad FIN AF: 0.000103

Gnomad MID AF: 0.0288

Gnomad NFE AF: 0.00314

Gnomad OTH AF: 0.00860

GnomAD4 exome AF: 0.00345 AC: 1745 AN: 505482 Hom.: 3 AF XY: 0.00357 AC XY: 971 AN XY: 271784

Gnomad4 AFR exome AF: 0.0153

Gnomad4 AMR exome AF: 0.00282

Gnomad4 ASJ exome AF: 0.00432

Gnomad4 EAS exome AF: 0.000292

Gnomad4 SAS exome AF: 0.00424

Gnomad4 FIN exome AF: 0.000394

Gnomad4 NFE exome AF: 0.00314

Gnomad4 OTH exome AF: 0.00576

GnomAD4 genome AF: 0.00490 AC: 707 AN: 144330 Hom.: 6 Cov.: 0 AF XY: 0.00466 AC XY: 326 AN XY: 69934

Gnomad4 AFR AF: 0.00917

Gnomad4 AMR AF: 0.00509

Gnomad4 ASJ AF: 0.00701

Gnomad4 EAS AF: 0.000419

Gnomad4 SAS AF: 0.00450

Gnomad4 FIN AF: 0.000103

Gnomad4 NFE AF: 0.00314

Gnomad4 OTH AF: 0.00902

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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;