Variant 5-140114194-GAC-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_005859.5(PURA):c.15_16del(p.Asp5GlufsTer195) 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 (★).

Frequency

Genomes: not found (cov: 31)

Consequence

PURA
NM_005859.5 frameshift

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 2.76

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]

PURA links:

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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 153 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 5-140114194-GAC-G is Pathogenic according to our data. Variant chr5-140114194-GAC-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1696911.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 linkuse as main transcript	c.15_16del	p.Asp5GlufsTer195	frameshift_variant	1/1	ENST00000331327.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PURA	ENST00000331327.5 linkuse as main transcript	c.15_16del	p.Asp5GlufsTer195	frameshift_variant	1/1		NM_005859.5	P1
PURA	ENST00000502351.1 linkuse as main transcript	c.15_16del	p.Asp5GlufsTer?	frameshift_variant	2/2	2
PURA	ENST00000505703.2 linkuse as main transcript	c.15_16del	p.Asp5GlufsTer?	frameshift_variant	2/2	3
PURA	ENST00000651386.1 linkuse as main transcript	c.15_16del	p.Asp5GlufsTer195	frameshift_variant	2/2			P1

Frequencies

GnomAD3 genomes

Cov.:

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

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

GeneDx

Jul 13, 2022

Frameshift variant in the C-terminus predicted to result in protein truncation, as the last 318 amino acids are lost and replaced with 194 incorrect amino acids, and other loss-of-function variants have been reported downstream in Human Gene Mutation Database (HGMD); Not observed in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing