17-28523792-TTCTCTCTCTCTCTCTCTCTCTCTCTCTC-TTCTCTCTCTCTCTCTCTCTC

Variant names:

• chr17-28523792-TTCTCTCTC-T
• rs10527420
• NM_001369369.1:c.-14-131_-14-124delTCTCTCTC

Variant summary

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

The NM_001369369.1(FOXN1):​c.-14-131_-14-124delTCTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 645,432 control chromosomes in the GnomAD database, including 4,502 homozygotes. Variant has been reported in ClinVar as Benign (★). The gene FOXN1 is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.22 (3772 hom., cov: 0)
  • Exomes 𝑓: 0.16 (730 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-TTCTCTCTC-T is Benign according to our data. Variant chr17-28523792-TTCTCTCTC-T is described in ClinVar as Benign. ClinVar VariationId is 1241419.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.309 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.-14-131_-14-124delTCTCTCTC		intron	N/A	NP_001356298.1	O15353
	FOXN1	NM_003593.3		c.-177_-170delTCTCTCTC		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_-14-156delTCTCTCTC		intron	N/A	ENSP00000464645.1	O15353
	RSKR	ENST00000481916.6	TSL:1	n.*1196-67691_*1196-67684delGAGAGAGA		intron	N/A	ENSP00000436369.2	Q96LW2-2
	FOXN1	ENST00000577936.2	TSL:4	c.-9-168_-9-161delTCTCTCTC		intron	N/A	ENSP00000462159.2	O15353

Frequencies

GnomAD3 genomes AF: 0.221 AC: 31829 AN: 143862 Hom.: 3767 Cov.: 0

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.0874

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.201

GnomAD4 exome AF: 0.164 AC: 82076 AN: 501470 Hom.: 730 AF XY: 0.162 AC XY: 43708 AN XY: 269600

African (AFR) AF: 0.251 AC: 3486 AN: 13916

American (AMR) AF: 0.105 AC: 2933 AN: 27920

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 3243 AN: 17404

East Asian (EAS) AF: 0.113 AC: 3458 AN: 30732

South Asian (SAS) AF: 0.143 AC: 8079 AN: 56498

European-Finnish (FIN) AF: 0.188 AC: 6599 AN: 35186

Middle Eastern (MID) AF: 0.205 AC: 490 AN: 2392

European-Non Finnish (NFE) AF: 0.170 AC: 49143 AN: 289690

Other (OTH) AF: 0.167 AC: 4645 AN: 27732

GnomAD4 genome AF: 0.221 AC: 31843 AN: 143962 Hom.: 3772 Cov.: 0 AF XY: 0.217 AC XY: 15154 AN XY: 69726

African (AFR) AF: 0.313 AC: 11785 AN: 37620

American (AMR) AF: 0.161 AC: 2298 AN: 14306

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 782 AN: 3422

East Asian (EAS) AF: 0.0874 AC: 416 AN: 4760

South Asian (SAS) AF: 0.155 AC: 688 AN: 4426

European-Finnish (FIN) AF: 0.217 AC: 2085 AN: 9620

Middle Eastern (MID) AF: 0.224 AC: 65 AN: 290

European-Non Finnish (NFE) AF: 0.197 AC: 13098 AN: 66648

Other (OTH) AF: 0.200 AC: 396 AN: 1984

Alfa AF: 0.179 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;