17-28523792-TTCTCTCTCTCTCTCTCTCTCTCTCTCTC-TTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTC

Variant names:

• chr17-28523792-T-TTCTCTCTCTC
• rs10527420
• NM_001369369.1:c.-14-133_-14-124dupTCTCTCTCTC

Variant summary

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

The NM_001369369.1(FOXN1):​c.-14-133_-14-124dupTCTCTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00238 in 649,726 control chromosomes in the GnomAD database, including 10 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0040 (8 hom., cov: 0)
  • Exomes 𝑓: 0.0019 (2 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 = 0.00397 (573/144290) while in subpopulation EAS AF= 0.0132 (63/4762). AF 95% confidence interval is 0.0106. There are 8 homozygotes in gnomad4. There are 274 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXN1	NM_001369369.1	c.-14-133_-14-124dupTCTCTCTCTC		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_-14-163insTCTCTCTCTC		intron_variant	Intron 1 of 8	1	NM_001369369.1	ENSP00000464645.1
RSKR	ENST00000481916.6	n.*1196-67684_*1196-67683insGAGAGAGAGA		intron_variant	Intron 7 of 7	1		ENSP00000436369.2
FOXN1	ENST00000577936.2	c.-9-169_-9-168insTCTCTCTCTC		intron_variant	Intron 1 of 8	4		ENSP00000462159.2

Frequencies

GnomAD3 genomes AF: 0.00393 AC: 566 AN: 144192 Hom.: 8 Cov.: 0

Gnomad AFR AF: 0.00694

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00440

Gnomad ASJ AF: 0.00963

Gnomad EAS AF: 0.0132

Gnomad SAS AF: 0.00135

Gnomad FIN AF: 0.000103

Gnomad MID AF: 0.00968

Gnomad NFE AF: 0.00174

Gnomad OTH AF: 0.0101

GnomAD4 exome AF: 0.00193 AC: 976 AN: 505436 Hom.: 2 AF XY: 0.00188 AC XY: 511 AN XY: 271766

Gnomad4 AFR exome AF: 0.00622

Gnomad4 AMR exome AF: 0.00292

Gnomad4 ASJ exome AF: 0.00319

Gnomad4 EAS exome AF: 0.00693

Gnomad4 SAS exome AF: 0.00200

Gnomad4 FIN exome AF: 0.000395

Gnomad4 NFE exome AF: 0.00119

Gnomad4 OTH exome AF: 0.00200

GnomAD4 genome AF: 0.00397 AC: 573 AN: 144290 Hom.: 8 Cov.: 0 AF XY: 0.00392 AC XY: 274 AN XY: 69920

Gnomad4 AFR AF: 0.00711

Gnomad4 AMR AF: 0.00440

Gnomad4 ASJ AF: 0.00963

Gnomad4 EAS AF: 0.0132

Gnomad4 SAS AF: 0.00135

Gnomad4 FIN AF: 0.000103

Gnomad4 NFE AF: 0.00174

Gnomad4 OTH AF: 0.0100

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;