19-15525513-C-G
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 14P and 1B. PM2PP3_StrongPP5_Very_StrongBS1_Supporting
The NM_173483.4(CYP4F22):c.177C>G(p.Phe59Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,459,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. F59F) has been classified as Likely benign.
Frequency
Consequence
NM_173483.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP4F22 | NM_173483.4 | c.177C>G | p.Phe59Leu | missense_variant | 3/14 | ENST00000269703.8 | |
CYP4F22 | XM_011527692.3 | c.177C>G | p.Phe59Leu | missense_variant | 4/15 | ||
CYP4F22 | XM_011527693.3 | c.177C>G | p.Phe59Leu | missense_variant | 3/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP4F22 | ENST00000269703.8 | c.177C>G | p.Phe59Leu | missense_variant | 3/14 | 2 | NM_173483.4 | P1 | |
CYP4F22 | ENST00000601005.2 | c.177C>G | p.Phe59Leu | missense_variant | 1/12 | 5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249736Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135138
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1459876Hom.: 0 Cov.: 32 AF XY: 0.00000551 AC XY: 4AN XY: 726336
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Autosomal recessive congenital ichthyosis 5 Pathogenic:5
Pathogenic, no assertion criteria provided | clinical testing | Institute for Human Genetics, University Medical Center Freiburg | Apr 23, 2018 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 15, 2020 | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Hadassah Hebrew University Medical Center | Jun 20, 2019 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City | Feb 05, 2020 | - - |
Pathogenic, criteria provided, single submitter | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 17, 2024 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Feb 15, 2022 | Published functional studies of F59L demonstrate a significant decrease of enzyme activity (Ohno et al., 2015); Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31168818, 16436457, 31130284, 33067036, 26056268) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at