17-28523792-T-TTCTCTC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001369369.1(FOXN1):c.-14-129_-14-124dup 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

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXN1	NM_001369369.1	c.-14-129_-14-124dup		intron_variant		ENST00000579795.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXN1	ENST00000579795.6	c.-14-129_-14-124dup		intron_variant		1	NM_001369369.1	P1
RSKR	ENST00000481916.6	c.*1196-67684_*1196-67683insGAGAGA		intron_variant, NMD_transcript_variant		1
FOXN1	ENST00000577936.2	c.-9-134_-9-129dup		intron_variant		4		P1

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

Gnomad4 AFR exome AF: 0.0252

Gnomad4 AMR exome AF: 0.0995

Gnomad4 ASJ exome AF: 0.0208

Gnomad4 EAS exome AF: 0.116

Gnomad4 SAS exome AF: 0.0311

Gnomad4 FIN exome AF: 0.0441

Gnomad4 NFE exome AF: 0.0329

Gnomad4 OTH exome AF: 0.0430

GnomAD4 genome AF: 0.0612 AC: 8799 AN: 143674 Hom.: 350 Cov.: 0 AF XY: 0.0622 AC XY: 4327 AN XY: 69520

Gnomad4 AFR AF: 0.0371

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.0426

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.0436

Gnomad4 FIN AF: 0.0619

Gnomad4 NFE AF: 0.0548

Gnomad4 OTH AF: 0.0605

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 24, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10527420; hg19: chr17-26850810;