chr5-140114218-GC-G
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_005859.5(PURA):c.38del(p.Ala13GlyfsTer65) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. A13A) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 31)
Consequence
PURA
NM_005859.5 frameshift
NM_005859.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.34
Genes affected
PURA (HGNC:9701): (purine rich element binding protein A) This gene product is a sequence-specific, single-stranded DNA-binding protein. It binds preferentially to the single strand of the purine-rich element termed PUR, which is present at origins of replication and in gene flanking regions in a variety of eukaryotes from yeasts through humans. Thus, it is implicated in the control of both DNA replication and transcription. Deletion of this gene has been associated with myelodysplastic syndrome and acute myelogenous leukemia. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 149 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 5-140114218-GC-G is Pathogenic according to our data. Variant chr5-140114218-GC-G is described in ClinVar as [Pathogenic]. Clinvar id is 817671.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PURA | NM_005859.5 | c.38del | p.Ala13GlyfsTer65 | frameshift_variant | 1/1 | ENST00000331327.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PURA | ENST00000331327.5 | c.38del | p.Ala13GlyfsTer65 | frameshift_variant | 1/1 | NM_005859.5 | P1 | ||
PURA | ENST00000651386.1 | c.38del | p.Ala13GlyfsTer65 | frameshift_variant | 2/2 | P1 | |||
PURA | ENST00000505703.2 | c.38del | p.Ala13GlyfsTer65 | frameshift_variant | 2/2 | 3 | |||
PURA | ENST00000502351.1 | c.38del | p.Ala13GlyfsTer? | frameshift_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Cov.: 12
GnomAD4 exome
Cov.:
12
GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jun 07, 2018 | The c.38delC variant in the PURA gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.38delC variant causes a frameshift starting with codon Alanine 13, changes this amino acid to a Glycine residue, and creates a premature Stop codon at position 65 of the new reading frame, denoted p.Ala13GlyfsX65. This variant is predicted to cause loss of normal protein function through protein truncation. The c.38delC variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.38delC as a pathogenic variant. - |
Computational scores
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at