rs793888537
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The NM_005859.5(PURA):c.4_8del(p.Ala2ProfsTer197) variant causes a frameshift change. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. A2A) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 31)
Consequence
PURA
NM_005859.5 frameshift
NM_005859.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.86
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 10 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 152 pathogenic variants in the truncated region.
PP5
?
Variant 5-140114184-GGCGGA-G is Pathogenic according to our data. Variant chr5-140114184-GGCGGA-G is described in ClinVar as [Pathogenic]. Clinvar id is 192344.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.4_8del | p.Ala2ProfsTer197 | frameshift_variant | 1/1 | ENST00000331327.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PURA | ENST00000331327.5 | c.4_8del | p.Ala2ProfsTer197 | frameshift_variant | 1/1 | NM_005859.5 | P1 | ||
PURA | ENST00000502351.1 | c.4_8del | p.Ala2ProfsTer? | frameshift_variant | 2/2 | 2 | |||
PURA | ENST00000505703.2 | c.4_8del | p.Ala2ProfsTer? | frameshift_variant | 2/2 | 3 | |||
PURA | ENST00000651386.1 | c.4_8del | p.Ala2ProfsTer197 | frameshift_variant | 2/2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
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 | Nov 01, 2016 | The c.4_8delGCGGA mutation in the PURA gene has not been reported previously as a disease causing variant nor as a benign polymorphism, to our knowledge. The c.4_8delGCGGA mutation causes a frameshift starting with codon Alanine 2, changes this amino acid to a Proline residue and creates a premature Stop codon at position 197 of the new reading frame, denoted p.Ala2ProfsX197. This mutation is predicted to cause loss of normal protein function through protein truncation. The c.4_8delGCGGA mutation was not observed in approximately 1800 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 c.4_8delGCGGA as a disease causing variant. This variant has been observed de novo with confirmed parentage. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at