chr19-15544257-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3PP5_Moderate
The NM_173483.4(CYP4F22):c.1114C>T(p.Arg372Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,613,730 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 (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000027 ( 0 hom. )
Consequence
CYP4F22
NM_173483.4 missense
NM_173483.4 missense
Scores
9
6
3
Clinical Significance
Conservation
PhyloP100: 1.36
Genes affected
CYP4F22 (HGNC:26820): (cytochrome P450 family 4 subfamily F member 22) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This gene is part of a cluster of cytochrome P450 genes on chromosome 19 and encodes an enzyme thought to play a role in the 12(R)-lipoxygenase pathway. Mutations in this gene are the cause of ichthyosis lamellar type 3. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.837
PP5
Variant 19-15544257-C-T is Pathogenic according to our data. Variant chr19-15544257-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 560328.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP4F22 | NM_173483.4 | c.1114C>T | p.Arg372Trp | missense_variant | 10/14 | ENST00000269703.8 | |
CYP4F22 | XM_011527692.3 | c.1114C>T | p.Arg372Trp | missense_variant | 11/15 | ||
CYP4F22 | XM_011527693.3 | c.1114C>T | p.Arg372Trp | missense_variant | 10/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP4F22 | ENST00000269703.8 | c.1114C>T | p.Arg372Trp | missense_variant | 10/14 | 2 | NM_173483.4 | P1 | |
CYP4F22 | ENST00000601005.2 | c.1114C>T | p.Arg372Trp | missense_variant | 8/12 | 5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151966Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250638Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135476
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GnomAD4 exome AF: 0.0000274 AC: 40AN: 1461764Hom.: 0 Cov.: 33 AF XY: 0.0000275 AC XY: 20AN XY: 727172
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GnomAD4 genome AF: 0.0000132 AC: 2AN: 151966Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74206
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive congenital ichthyosis 5 Pathogenic:2
Pathogenic, no assertion criteria provided | clinical testing | Institute for Human Genetics, University Medical Center Freiburg | Apr 23, 2018 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 27, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.
REVEL
Pathogenic
Sift
Pathogenic
D;.
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Loss of solvent accessibility (P = 0.0087);Loss of solvent accessibility (P = 0.0087);
MVP
MPC
ClinPred
D
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at