17-28523913-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_001369369.1(FOXN1):c.-14-43T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000514 in 1,611,150 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (4 hom.)
• Consequence: FOXN1 NM_001369369.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0420

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-28523913-T-C is Benign according to our data. Variant chr17-28523913-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1204197.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00269 (409/151886) while in subpopulation AFR AF= 0.00926 (383/41370). AF 95% confidence interval is 0.00849. There are 1 homozygotes in gnomad4. There are 163 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXN1	NM_001369369.1	c.-14-43T>C		intron_variant		ENST00000579795.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXN1	ENST00000579795.6	c.-14-43T>C		intron_variant		1	NM_001369369.1	P1
RSKR	ENST00000481916.6	c.*1196-67804A>G		intron_variant, NMD_transcript_variant		1
FOXN1	ENST00000577936.2	c.-9-48T>C		intron_variant		4		P1
FOXN1	ENST00000226247.2			upstream_gene_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.00269 AC: 409 AN: 151772 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00928

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00112

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: 0.0000589

Gnomad OTH AF: 0.00240

GnomAD4 exome AF: 0.000287 AC: 419 AN: 1459264 Hom.: 4 Cov.: 35 AF XY: 0.000249 AC XY: 181 AN XY: 726082

Gnomad4 AFR exome AF: 0.0100

Gnomad4 AMR exome AF: 0.000515

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000207

Gnomad4 OTH exome AF: 0.000497

GnomAD4 genome AF: 0.00269 AC: 409 AN: 151886 Hom.: 1 Cov.: 32 AF XY: 0.00220 AC XY: 163 AN XY: 74238

Gnomad4 AFR AF: 0.00926

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000589

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00202 Hom.: 0

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

Mar 27, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.4
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs532255609; hg19: chr17-26850931;