17-28523792-TTCTCTCTCTCTCTCTCTCTCTCTCTCTC-TTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTC

Variant names:

• chr17-28523792-T-TTCTCTC
• rs10527420
• NM_001369369.1:c.-14-129_-14-124dupTCTCTC

Variant summary

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

The NM_001369369.1(FOXN1):​c.-14-129_-14-124dupTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0463 in 641,378 control chromosomes in the GnomAD database, including 408 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.061 (350 hom., cov: 0)
  • Exomes 𝑓: 0.042 (58 hom.)
• Consequence: FOXN1 NM_001369369.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 17-28523792-T-TTCTCTC is Benign according to our data. Variant chr17-28523792-T-TTCTCTC is described in ClinVar as Benign. ClinVar VariationId is 1242877.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.138 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.-14-129_-14-124dupTCTCTC		intron	N/A	NP_001356298.1	O15353
	FOXN1	NM_003593.3		c.-178_-177insTCTCTC		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_-14-163insTCTCTC		intron	N/A	ENSP00000464645.1	O15353
	RSKR	ENST00000481916.6	TSL:1	n.*1196-67684_*1196-67683insGAGAGA		intron	N/A	ENSP00000436369.2	Q96LW2-2
	FOXN1	ENST00000577936.2	TSL:4	c.-9-169_-9-168insTCTCTC		intron	N/A	ENSP00000462159.2	O15353

Frequencies

GnomAD3 genomes AF: 0.0612 AC: 8783 AN: 143576 Hom.: 347 Cov.: 0

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.0586

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0426

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.0442

Gnomad FIN AF: 0.0619

Gnomad MID AF: 0.0353

Gnomad NFE AF: 0.0548

Gnomad OTH AF: 0.0612

GnomAD4 exome AF: 0.0419 AC: 20866 AN: 497704 Hom.: 58 AF XY: 0.0400 AC XY: 10721 AN XY: 267718

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

African (AFR) AF: 0.0252 AC: 350 AN: 13894

American (AMR) AF: 0.0995 AC: 2705 AN: 27182

Ashkenazi Jewish (ASJ) AF: 0.0208 AC: 363 AN: 17458

East Asian (EAS) AF: 0.116 AC: 3418 AN: 29360

South Asian (SAS) AF: 0.0311 AC: 1756 AN: 56516

European-Finnish (FIN) AF: 0.0441 AC: 1542 AN: 34962

Middle Eastern (MID) AF: 0.0259 AC: 62 AN: 2392

European-Non Finnish (NFE) AF: 0.0329 AC: 9489 AN: 288472

Other (OTH) AF: 0.0430 AC: 1181 AN: 27468

⚠️ 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: 0.0612 AC: 8799 AN: 143674 Hom.: 350 Cov.: 0 AF XY: 0.0622 AC XY: 4327 AN XY: 69520

African (AFR) AF: 0.0371 AC: 1395 AN: 37630

American (AMR) AF: 0.137 AC: 1940 AN: 14124

Ashkenazi Jewish (ASJ) AF: 0.0426 AC: 146 AN: 3424

East Asian (EAS) AF: 0.147 AC: 697 AN: 4726

South Asian (SAS) AF: 0.0436 AC: 193 AN: 4424

European-Finnish (FIN) AF: 0.0619 AC: 588 AN: 9502

Middle Eastern (MID) AF: 0.0414 AC: 12 AN: 290

European-Non Finnish (NFE) AF: 0.0548 AC: 3656 AN: 66684

Other (OTH) AF: 0.0605 AC: 120 AN: 1982

Alfa AF: 0.0398 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		0.097
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;