rs793888531
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM2PM5PP2PP3_StrongPP5
The NM_005859.5(PURA):c.305T>C(p.Leu102Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L102R) has been classified as Pathogenic.
Frequency
Consequence
NM_005859.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PURA | NM_005859.5 | c.305T>C | p.Leu102Pro | missense_variant | 1/1 | ENST00000331327.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PURA | ENST00000331327.5 | c.305T>C | p.Leu102Pro | missense_variant | 1/1 | NM_005859.5 | P1 | ||
PURA | ENST00000651386.1 | c.305T>C | p.Leu102Pro | missense_variant | 2/2 | P1 | |||
PURA | ENST00000505703.2 | c.305T>C | p.Leu102Pro | missense_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 33
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome Pathogenic:1Uncertain:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein | Jun 03, 2022 | ACMG classification criteria: PS4 supporting, PM2 moderated, PM5 moderated, PP2 supporting, PP3 supporting - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 27, 2022 | 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. 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 not expected to disrupt PURA protein function. ClinVar contains an entry for this variant (Variation ID: 522148). This variant has not been reported in the literature in individuals affected with PURA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 102 of the PURA protein (p.Leu102Pro). - |
Inborn genetic diseases Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 27, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at