NM_001369369.1:c.573T>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1

The NM_001369369.1(FOXN1):c.573T>C(p.His191His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000302 in 1,610,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

FOXN1
NM_001369369.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.257

Variant links:

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]

FOXN1 links:

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]

RSKR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 17-28524952-T-C is Benign according to our data. Variant chr17-28524952-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 392577.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.257 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000319 (465/1458194) while in subpopulation NFE AF= 0.000388 (431/1111380). AF 95% confidence interval is 0.000357. There are 0 homozygotes in gnomad4_exome. There are 221 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXN1	NM_001369369.1 link	c.573T>C	p.His191His	synonymous_variant	Exon 3 of 9	ENST00000579795.6	NP_001356298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FOXN1	ENST00000579795.6 link	c.573T>C	p.His191His	synonymous_variant	Exon 3 of 9	1	NM_001369369.1	ENSP00000464645.1	O15353
FOXN1	ENST00000226247.2 link	c.573T>C	p.His191His	synonymous_variant	Exon 2 of 8	1		ENSP00000226247.2	O15353
RSKR	ENST00000481916.6 link	n.*1196-68843A>G		intron_variant	Intron 7 of 7	1		ENSP00000436369.2	Q96LW2-2
FOXN1	ENST00000577936.2 link	c.573T>C	p.His191His	synonymous_variant	Exon 3 of 9	4		ENSP00000462159.2	O15353J3KRT9

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000146

AC:

AN:

245874

Hom.:

AF XY:

0.000150

AC XY:

AN XY:

133704

show subpopulations

Gnomad AFR exome

AF:

0.0000634

Gnomad AMR exome

AF:

0.000378

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000199

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000319

AC:

465

AN:

1458194

Hom.:

Cov.:

AF XY:

0.000305

AC XY:

221

AN XY:

725480

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.000336

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000193

Gnomad4 NFE exome

AF:

0.000388

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000138

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000193

Hom.:

Bravo

AF:

0.000178

EpiCase

AF:

0.000491

EpiControl

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 08, 2017

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

FOXN1-related disorder

Benign:1

May 11, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

T-cell immunodeficiency, congenital alopecia, and nail dystrophy

Benign:1

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

3.4

DANN

Benign

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over