chr5-140114218-GC-G

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

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 2.34
Variant links:
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
PURANM_005859.5 linkuse as main transcriptc.38del p.Ala13GlyfsTer65 frameshift_variant 1/1 ENST00000331327.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PURAENST00000331327.5 linkuse as main transcriptc.38del p.Ala13GlyfsTer65 frameshift_variant 1/1 NM_005859.5 P1
PURAENST00000651386.1 linkuse as main transcriptc.38del p.Ala13GlyfsTer65 frameshift_variant 2/2 P1
PURAENST00000505703.2 linkuse as main transcriptc.38del p.Ala13GlyfsTer65 frameshift_variant 2/23
PURAENST00000502351.1 linkuse as main transcriptc.38del p.Ala13GlyfsTer? frameshift_variant 2/22

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
12
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 submitterclinical testingGeneDxJun 07, 2018The 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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1581036001; hg19: chr5-139493803; API