5-140114195-AC-A

Position:

• chr5-140114195-AC-A

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_005859.5(PURA):​c.15del​(p.Asp5GlufsTer73) 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 Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PURA NM_005859.5 frameshift
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.19

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 Pathogenic. Variant got 11 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 22 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 5-140114195-AC-A is Pathogenic according to our data. Variant chr5-140114195-AC-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1184501.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PURA	NM_005859.5	c.15del	p.Asp5GlufsTer73	frameshift_variant	1/1	ENST00000331327.5	NP_005850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PURA	ENST00000331327.5	c.15del	p.Asp5GlufsTer73	frameshift_variant	1/1		NM_005859.5	ENSP00000332706	P1
PURA	ENST00000651386.1	c.15del	p.Asp5GlufsTer73	frameshift_variant	2/2			ENSP00000499133	P1
PURA	ENST00000505703.2	c.15del	p.Asp5GlufsTer73	frameshift_variant	2/2	3		ENSP00000498560
PURA	ENST00000502351.1	c.15del	p.Asp5GlufsTer?	frameshift_variant	2/2	2		ENSP00000498760

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 10

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

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

Likely pathogenic, no assertion criteria provided

clinical testing

Genomics England Pilot Project, Genomics England

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Computational scores

Source: dbNSFP v4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-139493780;