rs1554128999

chr5-140114185-GCGGAC-G

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_005859.5(PURA):c.7_11del(p.Asp3ArgfsTer196) variant causes a frameshift change. 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. A2A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PURA NM_005859.5 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 4.86

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 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 152 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 5-140114185-GCGGAC-G is Pathogenic according to our data. Variant chr5-140114185-GCGGAC-G is described in ClinVar as [Pathogenic]. Clinvar id is 520857.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.7_11del	p.Asp3ArgfsTer196	frameshift_variant	1/1	ENST00000331327.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PURA	ENST00000331327.5	c.7_11del	p.Asp3ArgfsTer196	frameshift_variant	1/1		NM_005859.5	P1
PURA	ENST00000502351.1	c.7_11del	p.Asp3ArgfsTer?	frameshift_variant	2/2	2
PURA	ENST00000505703.2	c.7_11del	p.Asp3ArgfsTer?	frameshift_variant	2/2	3
PURA	ENST00000651386.1	c.7_11del	p.Asp3ArgfsTer196	frameshift_variant	2/2			P1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2015

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1554128999; hg19: chr5-139493770;