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. The variant received -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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. The gene FOXN1 is included in the ClinGen Criteria Specification Registry.

• 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
• Publications: 1 publications found

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

Specifications for FOXN1 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 11 SD,AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369369.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXN1	NM_001369369.1	MANE Select	c.-14-137_-14-124delTCTCTCTCTCTCTC		intron	N/A	NP_001356298.1	O15353
	FOXN1	NM_003593.3		c.-177_-164delTCTCTCTCTCTCTC		upstream_gene	N/A	NP_003584.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXN1	ENST00000579795.6	TSL:1 MANE Select	c.-14-163_-14-150delTCTCTCTCTCTCTC		intron	N/A	ENSP00000464645.1	O15353
	RSKR	ENST00000481916.6	TSL:1	n.*1196-67697_*1196-67684delGAGAGAGAGAGAGA		intron	N/A	ENSP00000436369.2	Q96LW2-2
	FOXN1	ENST00000577936.2	TSL:4	c.-9-168_-9-155delTCTCTCTCTCTCTC		intron	N/A	ENSP00000462159.2	O15353

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

African (AFR) AF: 0.00256 AC: 36 AN: 14050

American (AMR) AF: 0.00506 AC: 142 AN: 28052

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 71 AN: 17572

East Asian (EAS) AF: 0.00120 AC: 37 AN: 30832

South Asian (SAS) AF: 0.00888 AC: 506 AN: 56988

European-Finnish (FIN) AF: 0.000592 AC: 21 AN: 35462

Middle Eastern (MID) AF: 0.00498 AC: 12 AN: 2408

European-Non Finnish (NFE) AF: 0.000852 AC: 249 AN: 292266

Other (OTH) AF: 0.00204 AC: 57 AN: 27972

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

African (AFR) AF: 0.00278 AC: 105 AN: 37742

American (AMR) AF: 0.00391 AC: 56 AN: 14334

Ashkenazi Jewish (ASJ) AF: 0.00204 AC: 7 AN: 3430

East Asian (EAS) AF: 0.00231 AC: 11 AN: 4768

South Asian (SAS) AF: 0.00811 AC: 36 AN: 4440

European-Finnish (FIN) AF: 0.000207 AC: 2 AN: 9668

Middle Eastern (MID) AF: 0.00690 AC: 2 AN: 290

European-Non Finnish (NFE) AF: 0.000763 AC: 51 AN: 66798

Other (OTH) AF: 0.00100 AC: 2 AN: 1996

Alfa AF: 0.00 Hom.: 106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.13

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10527420; hg19: chr17-26850810;