rs793888536
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_005859.5(PURA):c.419G>C(p.Arg140Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. R140R) has been classified as Benign.
Frequency
Consequence
NM_005859.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PURA | NM_005859.5 | c.419G>C | p.Arg140Pro | missense_variant | 1/1 | ENST00000331327.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PURA | ENST00000331327.5 | c.419G>C | p.Arg140Pro | missense_variant | 1/1 | NM_005859.5 | P1 | ||
PURA | ENST00000651386.1 | c.419G>C | p.Arg140Pro | missense_variant | 2/2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1453550Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 722864
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2022 | This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 140 of the PURA protein (p.Arg140Pro). This variant is not present in population databases (gnomAD no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 192343). This missense change has been observed in individual(s) with clinical features of PURA-related conditions (PMID: 29150892). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 11, 2018 | The R140P variant in the PURA gene has been reported previously in an individual with PURA-related disorder, however parental segregation was not performed (Lee et al., 2017). The R140P variant is not observed in large population cohorts (Lek et al., 2016). The R140P variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. In addition, R140P was observed in heterozygous state in a clinically unaffected relative of an individual referred for genetic testing at GeneDx. We interpret R140P as a variant of uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at