17-28523792-TTCTCTCTCTCTCTCTCTCTCTCTCTCTC-TTCTCTCTCTCTCTC

Variant names:

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

Variant summary

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

The NM_001369369.1(FOXN1):​c.-14-137_-14-124delTCTCTCTCTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00216 in 649,958 control chromosomes in the GnomAD database, including 11 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0022 (11 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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00188 (272/144356) while in subpopulation SAS AF= 0.00811 (36/4440). AF 95% confidence interval is 0.00602. There are 0 homozygotes in gnomad4. There are 143 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 11 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXN1	NM_001369369.1	c.-14-137_-14-124delTCTCTCTCTCTCTC		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_-14-150delTCTCTCTCTCTCTC		intron_variant	Intron 1 of 8	1	NM_001369369.1	ENSP00000464645.1
RSKR	ENST00000481916.6	n.*1196-67697_*1196-67684delGAGAGAGAGAGAGA		intron_variant	Intron 7 of 7	1		ENSP00000436369.2
FOXN1	ENST00000577936.2	c.-9-168_-9-155delTCTCTCTCTCTCTC		intron_variant	Intron 1 of 8	4		ENSP00000462159.2
FOXN1	ENST00000226247.2	c.-177_-164delTCTCTCTCTCTCTC		upstream_gene_variant		1		ENSP00000226247.2

Frequencies

GnomAD3 genomes AF: 0.00189 AC: 272 AN: 144256 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00279

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00384

Gnomad ASJ AF: 0.00204

Gnomad EAS AF: 0.00230

Gnomad SAS AF: 0.00832

Gnomad FIN AF: 0.000207

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.000763

Gnomad OTH AF: 0.00101

GnomAD4 exome AF: 0.00224 AC: 1131 AN: 505602 Hom.: 11 AF XY: 0.00268 AC XY: 729 AN XY: 271846

Gnomad4 AFR exome AF: 0.00256

Gnomad4 AMR exome AF: 0.00506

Gnomad4 ASJ exome AF: 0.00404

Gnomad4 EAS exome AF: 0.00120

Gnomad4 SAS exome AF: 0.00888

Gnomad4 FIN exome AF: 0.000592

Gnomad4 NFE exome AF: 0.000852

Gnomad4 OTH exome AF: 0.00204

GnomAD4 genome AF: 0.00188 AC: 272 AN: 144356 Hom.: 0 Cov.: 0 AF XY: 0.00204 AC XY: 143 AN XY: 69950

Gnomad4 AFR AF: 0.00278

Gnomad4 AMR AF: 0.00391

Gnomad4 ASJ AF: 0.00204

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.00811

Gnomad4 FIN AF: 0.000207

Gnomad4 NFE AF: 0.000763

Gnomad4 OTH AF: 0.00100

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;