17-28523792-TTCTCTCTCTCTCTCTCTCTCTCTCTCTC-TTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTC

Variant names:

• chr17-28523792-T-TTCTCTCTCTCTCTC
• rs10527420
• NM_001369369.1:c.-14-137_-14-124dupTCTCTCTCTCTCTC

Variant summary

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

The NM_001369369.1(FOXN1):​c.-14-137_-14-124dupTCTCTCTCTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000363 in 650,380 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 0.00087 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00022 (0 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 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 = 0.000873 (126/144328) while in subpopulation AFR AF= 0.00225 (85/37732). AF 95% confidence interval is 0.00187. There are 0 homozygotes in gnomad4. There are 60 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.-14-137_-14-124dupTCTCTCTCTCTCTC		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_-14-163insTCTCTCTCTCTCTC		intron_variant	Intron 1 of 8	1	NM_001369369.1	ENSP00000464645.1
RSKR	ENST00000481916.6	n.*1196-67684_*1196-67683insGAGAGAGAGAGAGA		intron_variant	Intron 7 of 7	1		ENSP00000436369.2
FOXN1	ENST00000577936.2	c.-9-169_-9-168insTCTCTCTCTCTCTC		intron_variant	Intron 1 of 8	4		ENSP00000462159.2
FOXN1	ENST00000226247.2	c.-178_-177insTCTCTCTCTCTCTC		upstream_gene_variant		1		ENSP00000226247.2

Frequencies

GnomAD3 genomes AF: 0.000881 AC: 127 AN: 144228 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00226

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000978

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000838

Gnomad SAS AF: 0.000675

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0129

Gnomad NFE AF: 0.000254

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000217 AC: 110 AN: 506052 Hom.: 0 AF XY: 0.000239 AC XY: 65 AN XY: 272078

Gnomad4 AFR exome AF: 0.00171

Gnomad4 AMR exome AF: 0.000214

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000195

Gnomad4 SAS exome AF: 0.000508

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000133

Gnomad4 OTH exome AF: 0.000214

GnomAD4 genome AF: 0.000873 AC: 126 AN: 144328 Hom.: 0 Cov.: 0 AF XY: 0.000858 AC XY: 60 AN XY: 69934

Gnomad4 AFR AF: 0.00225

Gnomad4 AMR AF: 0.000977

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000840

Gnomad4 SAS AF: 0.000676

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000255

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;