rs746471609

Positions:

• chr17-28527272-C-A
• chr17-28527272-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001369369.1(FOXN1):​c.610C>A​(p.Pro204Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FOXN1 NM_001369369.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09247914).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXN1	NM_001369369.1	c.610C>A	p.Pro204Thr	missense_variant	4/9	ENST00000579795.6	NP_001356298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXN1	ENST00000579795.6	c.610C>A	p.Pro204Thr	missense_variant	4/9	1	NM_001369369.1	ENSP00000464645.1
FOXN1	ENST00000226247.2	c.610C>A	p.Pro204Thr	missense_variant	3/8	1		ENSP00000226247.2
RSKR	ENST00000481916.6	n.*1196-71163G>T		intron_variant		1		ENSP00000436369.2
FOXN1	ENST00000577936.2	c.610C>A	p.Pro204Thr	missense_variant	4/9	4		ENSP00000462159.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.16	T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.036
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.69	.;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.092	T;T
MetaSVM	Uncertain	0.15	D
MutationAssessor	Benign	0.34	N;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.33	.;N
REVEL	Benign	0.24
Sift	Benign	0.21	.;T
Sift4G	Benign	0.20	T;T
Polyphen		0.010	B;B
Vest4		0.091
MutPred		0.46		Gain of glycosylation at P204 (P = 0.0379);Gain of glycosylation at P204 (P = 0.0379);
MVP		0.44
MPC		0.16
ClinPred		0.40	T
GERP RS		5.6
Varity_R		0.12
gMVP		0.29

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: rs746471609; hg19: chr17-26854290;