chr17-28523792-T-TTCTCTC

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

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 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 rank	MANE	Protein	UniProt
FOXN1	NM_001369369.1	c.-14-129_-14-124dupTCTCTC		intron_variant	Intron 1 of 8	ENST00000579795.6	NP_001356298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXN1	ENST00000579795.6	c.-14-164_-14-163insTCTCTC		intron_variant	Intron 1 of 8	1	NM_001369369.1	ENSP00000464645.1
RSKR	ENST00000481916.6	n.*1196-67684_*1196-67683insGAGAGA		intron_variant	Intron 7 of 7	1		ENSP00000436369.2
FOXN1	ENST00000577936.2	c.-9-169_-9-168insTCTCTC		intron_variant	Intron 1 of 8	4		ENSP00000462159.2
FOXN1	ENST00000226247.2	c.-178_-177insTCTCTC		upstream_gene_variant		1		ENSP00000226247.2

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 AC: 350 AN: 13894

Gnomad4 AMR exome AF: 0.0995 AC: 2705 AN: 27182

Gnomad4 ASJ exome AF: 0.0208 AC: 363 AN: 17458

Gnomad4 EAS exome AF: 0.116 AC: 3418 AN: 29360

Gnomad4 SAS exome AF: 0.0311 AC: 1756 AN: 56516

Gnomad4 FIN exome AF: 0.0441 AC: 1542 AN: 34962

Gnomad4 NFE exome AF: 0.0329 AC: 9489 AN: 288472

Gnomad4 Remaining exome AF: 0.0430 AC: 1181 AN: 27468

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 AC: 0.0370715 AN: 0.0370715

Gnomad4 AMR AF: 0.137 AC: 0.137355 AN: 0.137355

Gnomad4 ASJ AF: 0.0426 AC: 0.0426402 AN: 0.0426402

Gnomad4 EAS AF: 0.147 AC: 0.147482 AN: 0.147482

Gnomad4 SAS AF: 0.0436 AC: 0.0436257 AN: 0.0436257

Gnomad4 FIN AF: 0.0619 AC: 0.0618817 AN: 0.0618817

Gnomad4 NFE AF: 0.0548 AC: 0.0548257 AN: 0.0548257

Gnomad4 OTH AF: 0.0605 AC: 0.0605449 AN: 0.0605449

Alfa AF: 0.0398 Hom.: 106

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 24, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mutation Taster		=100/0	polymorphism (auto)

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;