rs923665124
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_005859.5(PURA):c.43C>A(p.Leu15Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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. L15P) has been classified as Uncertain significance.
Frequency
Consequence
NM_005859.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PURA | NM_005859.5 | c.43C>A | p.Leu15Met | missense_variant | 1/1 | ENST00000331327.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PURA | ENST00000331327.5 | c.43C>A | p.Leu15Met | missense_variant | 1/1 | NM_005859.5 | P1 | ||
PURA | ENST00000651386.1 | c.43C>A | p.Leu15Met | missense_variant | 2/2 | P1 | |||
PURA | ENST00000505703.2 | c.43C>A | p.Leu15Met | missense_variant | 2/2 | 3 | |||
PURA | ENST00000502351.1 | c.43C>A | p.Leu15Met | missense_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 921798Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0AN XY: 442042
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 12, 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. 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: "Not Available"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 565516). This variant has not been reported in the literature in individuals affected with PURA-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 15 of the PURA protein (p.Leu15Met). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at