chr5-140114486-T-G
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM2PM5PP2PP3_StrongPP5_Moderate
The NM_005859.5(PURA):c.305T>G(p.Leu102Arg) 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 Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L102P) has been classified as Likely pathogenic.
Frequency
Consequence
NM_005859.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PURA | NM_005859.5 | c.305T>G | p.Leu102Arg | missense_variant | 1/1 | ENST00000331327.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PURA | ENST00000331327.5 | c.305T>G | p.Leu102Arg | missense_variant | 1/1 | NM_005859.5 | P1 | ||
PURA | ENST00000651386.1 | c.305T>G | p.Leu102Arg | missense_variant | 2/2 | P1 | |||
PURA | ENST00000505703.2 | c.305T>G | p.Leu102Arg | missense_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jun 03, 2015 | p.Leu102Arg (CTC>CGC): c.305 T>G in exon 1 in the PURA gene (NM_005859.4). The L102R variant in the PURA gene has not been reported previously as a disease-causing mutation nor as a benign polymorphism, to our knowledge. The L102R variant is a non-conservative amino acid substitution as these residues differ in polarity, charge, size and/or other properties and is more likely to impact secondary structure. This change occurs at a residue that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. The L102R variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret L102R as a disease-causing mutation. The variant has been observed de novo with confirmed parentage. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at