rs759625169
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_020964.3(EPG5):c.2461C>T(p.Arg821Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,726 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 Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_020964.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPG5 | NM_020964.3 | c.2461C>T | p.Arg821Ter | stop_gained | 13/44 | ENST00000282041.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPG5 | ENST00000282041.11 | c.2461C>T | p.Arg821Ter | stop_gained | 13/44 | 1 | NM_020964.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152076Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249396Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135316
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461650Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727142
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152076Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74286
ClinVar
Submissions by phenotype
Vici syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | This sequence change creates a premature translational stop signal (p.Arg821*) in the EPG5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EPG5 are known to be pathogenic (PMID: 23222957, 23674064). This variant is present in population databases (rs759625169, gnomAD 0.005%). This premature translational stop signal has been observed in individual(s) with clinical features of Vici syndrome (PMID: 28615637). ClinVar contains an entry for this variant (Variation ID: 267454). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at