17-28523792-TTCTCTCTCTCTCTCTCTCTCTCTCTCTC-TTCTCTCTC

Variant names:

• chr17-28523792-TTCTCTCTCTCTCTCTCTCTC-T
• rs10527420
• NM_001369369.1:c.-14-143_-14-124delTCTCTCTCTCTCTCTCTCTC

Variant summary

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

The NM_001369369.1(FOXN1):​c.-14-143_-14-124delTCTCTCTCTCTCTCTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000667 in 641,554 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000069 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00084 (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 nfe. gnomad4_exome allele frequency = 0.000841 (418/497220) while in subpopulation NFE AF= 0.000931 (267/286862). AF 95% confidence interval is 0.000839. There are 0 homozygotes in gnomad4_exome. There are 245 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXN1	NM_001369369.1	c.-14-143_-14-124delTCTCTCTCTCTCTCTCTCTC		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_-14-144delTCTCTCTCTCTCTCTCTCTC		intron_variant	Intron 1 of 8	1	NM_001369369.1	ENSP00000464645.1
RSKR	ENST00000481916.6	n.*1196-67703_*1196-67684delGAGAGAGAGAGAGAGAGAGA		intron_variant	Intron 7 of 7	1		ENSP00000436369.2
FOXN1	ENST00000577936.2	c.-9-168_-9-149delTCTCTCTCTCTCTCTCTCTC		intron_variant	Intron 1 of 8	4		ENSP00000462159.2

Frequencies

GnomAD3 genomes AF: 0.0000693 AC: 10 AN: 144234 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000797

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000105

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000841 AC: 418 AN: 497220 Hom.: 0 AF XY: 0.000916 AC XY: 245 AN XY: 267386

Gnomad4 AFR exome AF: 0.000573

Gnomad4 AMR exome AF: 0.000646

Gnomad4 ASJ exome AF: 0.000869

Gnomad4 EAS exome AF: 0.000429

Gnomad4 SAS exome AF: 0.000747

Gnomad4 FIN exome AF: 0.00115

Gnomad4 NFE exome AF: 0.000931

Gnomad4 OTH exome AF: 0.000473

GnomAD4 genome AF: 0.0000693 AC: 10 AN: 144334 Hom.: 0 Cov.: 0 AF XY: 0.0000429 AC XY: 3 AN XY: 69938

Gnomad4 AFR AF: 0.0000795

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000105

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;