chr19-15525497-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_173483.4(CYP4F22):c.161G>A(p.Arg54His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,613,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R54C) has been classified as Uncertain significance.
Frequency
Consequence
NM_173483.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP4F22 | NM_173483.4 | c.161G>A | p.Arg54His | missense_variant | 3/14 | ENST00000269703.8 | |
CYP4F22 | XM_011527692.3 | c.161G>A | p.Arg54His | missense_variant | 4/15 | ||
CYP4F22 | XM_011527693.3 | c.161G>A | p.Arg54His | missense_variant | 3/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP4F22 | ENST00000269703.8 | c.161G>A | p.Arg54His | missense_variant | 3/14 | 2 | NM_173483.4 | P1 | |
CYP4F22 | ENST00000601005.2 | c.161G>A | p.Arg54His | missense_variant | 1/12 | 5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152160Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000132 AC: 33AN: 250562Hom.: 0 AF XY: 0.000177 AC XY: 24AN XY: 135488
GnomAD4 exome AF: 0.000107 AC: 157AN: 1461032Hom.: 0 Cov.: 32 AF XY: 0.000106 AC XY: 77AN XY: 726850
GnomAD4 genome AF: 0.0000854 AC: 13AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74336
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 22, 2023 | This variant is present in population databases (rs139927884, gnomAD 0.03%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 54 of the CYP4F22 protein (p.Arg54His). This variant has not been reported in the literature in individuals affected with CYP4F22-related conditions. ClinVar contains an entry for this variant (Variation ID: 2061051). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at