17-28523792-TTCTCTCTC-T

Position:

• chr17-28523792-TTCTCTCTC-T

Variant summary

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

The NM_001369369.1(FOXN1):​c.-14-131_-14-124del 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 (★).

• 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

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-TTCTCTCTC-T is Benign according to our data. Variant chr17-28523792-TTCTCTCTC-T is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXN1	NM_001369369.1	c.-14-131_-14-124del		intron_variant		ENST00000579795.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXN1	ENST00000579795.6	c.-14-131_-14-124del		intron_variant		1	NM_001369369.1	P1
RSKR	ENST00000481916.6	c.*1196-67691_*1196-67684del		intron_variant, NMD_transcript_variant		1
FOXN1	ENST00000577936.2	c.-9-136_-9-129del		intron_variant		4		P1

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

Gnomad4 AFR exome AF: 0.251

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.186

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.170

Gnomad4 OTH exome AF: 0.167

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

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.0874

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.200

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 20, 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;