rs786204833

chr5-140114904-CGT-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_Strong PP5

The NM_005859.5(PURA):c.726_727del(p.Phe243TyrfsTer50) variant causes a frameshift change. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. V242V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PURA NM_005859.5 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.25

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 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 13 pathogenic variants in the truncated region.
• PP5: Variant 5-140114904-CGT-C is Pathogenic according to our data. Variant chr5-140114904-CGT-C is described in ClinVar as [Pathogenic]. Clinvar id is 189317.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PURA	NM_005859.5	c.726_727del	p.Phe243TyrfsTer50	frameshift_variant	1/1	ENST00000331327.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PURA	ENST00000331327.5	c.726_727del	p.Phe243TyrfsTer50	frameshift_variant	1/1		NM_005859.5	P1
PURA	ENST00000651386.1	c.726_727del	p.Phe243TyrfsTer50	frameshift_variant	2/2			P1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 01, 2014

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs786204833; hg19: chr5-139494489;