rs119103283
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PM5PP3_Strong
The NM_207352.4(CYP4V2):c.332T>A(p.Ile111Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,322 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I111T) has been classified as Pathogenic.
Frequency
Consequence
NM_207352.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CYP4V2 | NM_207352.4 | c.332T>A | p.Ile111Asn | missense_variant | 3/11 | ENST00000378802.5 | NP_997235.3 | |
CYP4V2 | XM_005262935.5 | c.332T>A | p.Ile111Asn | missense_variant | 3/11 | XP_005262992.1 | ||
CYP4V2 | XM_047450077.1 | c.18-933T>A | intron_variant | XP_047306033.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CYP4V2 | ENST00000378802.5 | c.332T>A | p.Ile111Asn | missense_variant | 3/11 | 1 | NM_207352.4 | ENSP00000368079.4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459322Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726160
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 14, 2021 | 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. This variant disrupts the p.Ile111 amino acid residue in CYP4V2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15042513, 23221965, 29691984). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CYP4V2 protein function. This variant has not been reported in the literature in individuals affected with CYP4V2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with asparagine at codon 111 of the CYP4V2 protein (p.Ile111Asn). The isoleucine residue is moderately conserved and there is a large physicochemical difference between isoleucine and asparagine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.