rs201402291
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_020964.3(EPG5):c.494C>T(p.Pro165Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. P165A) has been classified as Uncertain significance.
Frequency
Consequence
NM_020964.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPG5 | NM_020964.3 | c.494C>T | p.Pro165Leu | missense_variant | 2/44 | ENST00000282041.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPG5 | ENST00000282041.11 | c.494C>T | p.Pro165Leu | missense_variant | 2/44 | 1 | NM_020964.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 152090Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000482 AC: 12AN: 249044Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135130
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461374Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 726968
GnomAD4 genome ? AF: 0.000138 AC: 21AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74406
ClinVar
Submissions by phenotype
Vici syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 165 of the EPG5 protein (p.Pro165Leu). This variant is present in population databases (rs201402291, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with EPG5-related conditions. ClinVar contains an entry for this variant (Variation ID: 466253). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine 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