17-28523792-T-TTCTC

Position:

• chr17-28523792-T-TTCTC

Variant summary

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

The NM_001369369.1(FOXN1):​c.-14-127_-14-124dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 642,398 control chromosomes in the GnomAD database, including 63 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (38 hom., cov: 0)
  • Exomes 𝑓: 0.017 (25 hom.)
• Consequence: FOXN1 NM_001369369.1 intron
• Clinical Significance: Likely 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-TTCTC is Benign according to our data. Variant chr17-28523792-T-TTCTC is described in ClinVar as [Likely_benign]. Clinvar id is 1706676.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXN1	NM_001369369.1	c.-14-127_-14-124dup		intron_variant		ENST00000579795.6	NP_001356298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXN1	ENST00000579795.6	c.-14-127_-14-124dup		intron_variant		1	NM_001369369.1	ENSP00000464645	P1
RSKR	ENST00000481916.6	c.*1196-67684_*1196-67683insGAGA		intron_variant, NMD_transcript_variant		1		ENSP00000436369
FOXN1	ENST00000577936.2	c.-9-132_-9-129dup		intron_variant		4		ENSP00000462159	P1

Frequencies

GnomAD3 genomes AF: 0.0173 AC: 2498 AN: 144088 Hom.: 38 Cov.: 0

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0485

Gnomad ASJ AF: 0.00554

Gnomad EAS AF: 0.0134

Gnomad SAS AF: 0.0133

Gnomad FIN AF: 0.00891

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.0182

GnomAD4 exome AF: 0.0172 AC: 8557 AN: 498212 Hom.: 25 AF XY: 0.0164 AC XY: 4392 AN XY: 268100

Gnomad4 AFR exome AF: 0.0223

Gnomad4 AMR exome AF: 0.0639

Gnomad4 ASJ exome AF: 0.00648

Gnomad4 EAS exome AF: 0.0309

Gnomad4 SAS exome AF: 0.0146

Gnomad4 FIN exome AF: 0.0153

Gnomad4 NFE exome AF: 0.0126

Gnomad4 OTH exome AF: 0.0169

GnomAD4 genome AF: 0.0174 AC: 2504 AN: 144186 Hom.: 38 Cov.: 0 AF XY: 0.0179 AC XY: 1248 AN XY: 69858

Gnomad4 AFR AF: 0.0222

Gnomad4 AMR AF: 0.0485

Gnomad4 ASJ AF: 0.00554

Gnomad4 EAS AF: 0.0134

Gnomad4 SAS AF: 0.0133

Gnomad4 FIN AF: 0.00891

Gnomad4 NFE AF: 0.0106

Gnomad4 OTH AF: 0.0185

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 24, 2019

See Variant Classification Assertion Criteria. -

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;