chr17-28523792-T-TTCTCTCTCTCTCTCTCTCTCTCTCTC

Variant names:

• chr17-28523792-T-TTCTCTCTCTCTCTCTCTCTCTCTCTC
• rs10527420
• NM_001369369.1:c.-14-149_-14-124dupTCTCTCTCTCTCTCTCTCTCTCTCTC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001369369.1(FOXN1):​c.-14-149_-14-124dupTCTCTCTCTCTCTCTCTCTCTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_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.

• Frequency:
  • Genomes: 𝑓 0.0000069 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000020 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXN1 NM_001369369.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970
• 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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.-14-149_-14-124dupTCTCTCTCTCTCTCTCTCTCTCTCTC		intron	N/A	NP_001356298.1	O15353
	FOXN1	NM_003593.3		c.-178_-177insTCTCTCTCTCTCTCTCTCTCTCTCTC		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.-14-164_-14-163insTCTCTCTCTCTCTCTCTCTCTCTCTC		intron	N/A	ENSP00000464645.1	O15353
	RSKR	ENST00000481916.6	TSL:1	n.*1196-67684_*1196-67683insGAGAGAGAGAGAGAGAGAGAGAGAGA		intron	N/A	ENSP00000436369.2	Q96LW2-2
	FOXN1	ENST00000577936.2	TSL:4	c.-9-169_-9-168insTCTCTCTCTCTCTCTCTCTCTCTCTC		intron	N/A	ENSP00000462159.2	O15353

Frequencies

GnomAD3 genomes AF: 0.00000693 AC: 1 AN: 144256 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000198 AC: 1 AN: 506164 Hom.: 0 AF XY: 0.00000367 AC XY: 1 AN XY: 272142

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 14056

American (AMR) AF: 0.00 AC: 0 AN: 28078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17594

East Asian (EAS) AF: 0.00 AC: 0 AN: 30854

South Asian (SAS) AF: 0.00 AC: 0 AN: 57046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2412

European-Non Finnish (NFE) AF: 0.00000342 AC: 1 AN: 292622

Other (OTH) AF: 0.00 AC: 0 AN: 27998

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000693 AC: 1 AN: 144256 Hom.: 0 Cov.: 0 AF XY: 0.0000143 AC XY: 1 AN XY: 69838

African (AFR) AF: 0.0000266 AC: 1 AN: 37634

American (AMR) AF: 0.00 AC: 0 AN: 14316

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3430

East Asian (EAS) AF: 0.00 AC: 0 AN: 4780

South Asian (SAS) AF: 0.00 AC: 0 AN: 4446

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9668

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66804

Other (OTH) AF: 0.00 AC: 0 AN: 1976

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.097

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;