rs61749867
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001369369.1(FOXN1):c.1288C>T(p.Pro430Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0422 in 1,614,016 control chromosomes in the GnomAD database, including 1,893 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P430L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001369369.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXN1 | NM_001369369.1 | c.1288C>T | p.Pro430Ser | missense_variant | 8/9 | ENST00000579795.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXN1 | ENST00000579795.6 | c.1288C>T | p.Pro430Ser | missense_variant | 8/9 | 1 | NM_001369369.1 | P1 | |
FOXN1 | ENST00000226247.2 | c.1288C>T | p.Pro430Ser | missense_variant | 7/8 | 1 | P1 | ||
RSKR | ENST00000481916.6 | c.*1195+69192G>A | intron_variant, NMD_transcript_variant | 1 | |||||
FOXN1 | ENST00000577936.2 | c.1288C>T | p.Pro430Ser | missense_variant | 8/9 | 4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0297 AC: 4515AN: 152156Hom.: 111 Cov.: 33
GnomAD3 exomes AF: 0.0308 AC: 7734AN: 250710Hom.: 207 AF XY: 0.0309 AC XY: 4193AN XY: 135556
GnomAD4 exome AF: 0.0435 AC: 63586AN: 1461742Hom.: 1782 Cov.: 35 AF XY: 0.0421 AC XY: 30581AN XY: 727172
GnomAD4 genome ? AF: 0.0297 AC: 4515AN: 152274Hom.: 111 Cov.: 33 AF XY: 0.0308 AC XY: 2290AN XY: 74456
ClinVar
Submissions by phenotype
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 10, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 07, 2016 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
T-cell immunodeficiency, congenital alopecia, and nail dystrophy Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at