rs793888533
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PM4PP3PP5_Moderate
The NM_005859.5(PURA):c.302_310del(p.Thr101_Ser103del) variant causes a inframe deletion change involving the alteration of a 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. T101T) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
PURA
NM_005859.5 inframe_deletion
NM_005859.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.81
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 Likely_pathogenic. Variant got 9 ACMG points.
PM1
?
In a hotspot region, there are 4 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 2 benign, 1 uncertain in NM_005859.5
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_005859.5.
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
?
Variant 5-140114481-TACTCTCTCC-T is Pathogenic according to our data. Variant chr5-140114481-TACTCTCTCC-T is described in ClinVar as [Pathogenic]. Clinvar id is 192340.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.302_310del | p.Thr101_Ser103del | inframe_deletion | 1/1 | ENST00000331327.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PURA | ENST00000331327.5 | c.302_310del | p.Thr101_Ser103del | inframe_deletion | 1/1 | NM_005859.5 | P1 | ||
PURA | ENST00000505703.2 | c.302_310del | p.Thr101_Ser103del | inframe_deletion | 2/2 | 3 | |||
PURA | ENST00000651386.1 | c.302_310del | p.Thr101_Ser103del | inframe_deletion | 2/2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 17, 2021 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Feb 12, 2015 | c.302_310delCTCTCTCCA: p.Thr101_Ser103del in exon 1 in the PURA gene (NM_005859.4). The normal sequence with the bases that are deleted in braces is: CTTA{CTCTCTCCA}TGTC. The c.302_310delCTCTCTCCA mutation in the PURA gene has not been reported previously as a disease-causing mutation nor as a benign polymorphism, to our knowledge. The c.302_310delCTCTCTCCA mutation 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. The c.302_310delCTCTCTCCA mutation causes an in-frame deletion of three amino acids in exon 1 of the PURA gene; these amino acids are well-conserved across species. We interpret c.302_310delCTCTCTCCA as a disease-causing mutation associated with PURA-related disorders. 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