17-28523792-TTCTCTCTCTCTCTCTCTCTCTCTCTCTC-TTCTCTCTCTCTC

Variant names:

• chr17-28523792-TTCTCTCTCTCTCTCTC-T
• rs10527420
• NM_001369369.1:c.-14-139_-14-124delTCTCTCTCTCTCTCTC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001369369.1(FOXN1):​c.-14-139_-14-124delTCTCTCTCTCTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 650,148 control chromosomes in the GnomAD database, including 49,099 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. Variant has been reported in ClinVar as Benign (★). The gene FOXN1 is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.56 (23563 hom., cov: 0)
  • Exomes 𝑓: 0.48 (25536 hom.)
• Consequence: FOXN1 NM_001369369.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 17-28523792-TTCTCTCTCTCTCTCTC-T is Benign according to our data. Variant chr17-28523792-TTCTCTCTCTCTCTCTC-T is described in ClinVar as Benign. ClinVar VariationId is 1266250.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

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.-14-139_-14-124delTCTCTCTCTCTCTCTC		intron	N/A	NP_001356298.1	O15353
	FOXN1	NM_003593.3		c.-177_-162delTCTCTCTCTCTCTCTC		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_-14-148delTCTCTCTCTCTCTCTC		intron	N/A	ENSP00000464645.1	O15353
	RSKR	ENST00000481916.6	TSL:1	n.*1196-67699_*1196-67684delGAGAGAGAGAGAGAGA		intron	N/A	ENSP00000436369.2	Q96LW2-2
	FOXN1	ENST00000577936.2	TSL:4	c.-9-168_-9-153delTCTCTCTCTCTCTCTC		intron	N/A	ENSP00000462159.2	O15353

Frequencies

GnomAD3 genomes AF: 0.563 AC: 81234 AN: 144262 Hom.: 23568 Cov.: 0

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.569

GnomAD4 exome AF: 0.475 AC: 240313 AN: 505786 Hom.: 25536 AF XY: 0.475 AC XY: 129229 AN XY: 271952

African (AFR) AF: 0.320 AC: 4490 AN: 14050

American (AMR) AF: 0.431 AC: 12087 AN: 28056

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 8770 AN: 17574

East Asian (EAS) AF: 0.467 AC: 14396 AN: 30838

South Asian (SAS) AF: 0.440 AC: 25067 AN: 57010

European-Finnish (FIN) AF: 0.509 AC: 18057 AN: 35472

Middle Eastern (MID) AF: 0.465 AC: 1118 AN: 2406

European-Non Finnish (NFE) AF: 0.490 AC: 143245 AN: 292404

Other (OTH) AF: 0.468 AC: 13083 AN: 27976

GnomAD4 genome AF: 0.563 AC: 81243 AN: 144362 Hom.: 23563 Cov.: 0 AF XY: 0.565 AC XY: 39559 AN XY: 69958

African (AFR) AF: 0.377 AC: 14246 AN: 37738

American (AMR) AF: 0.547 AC: 7848 AN: 14344

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2166 AN: 3430

East Asian (EAS) AF: 0.668 AC: 3187 AN: 4772

South Asian (SAS) AF: 0.578 AC: 2565 AN: 4436

European-Finnish (FIN) AF: 0.653 AC: 6317 AN: 9670

Middle Eastern (MID) AF: 0.583 AC: 169 AN: 290

European-Non Finnish (NFE) AF: 0.646 AC: 43122 AN: 66796

Other (OTH) AF: 0.566 AC: 1130 AN: 1996

Alfa AF: 0.678 Hom.: 106

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

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;