5-140114171-A-AGCGCAGCATCATG

Variant names:

• chr5-140114171-A-AGCGCAGCATCATG
• NM_005859.5:c.-7_6dupCAGCATCATGGCG

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_005859.5(PURA):​c.-7_6dupCAGCATCATGGCG​(p.Asp3fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PURA NM_005859.5 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209

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 10 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 23 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PURA	NM_005859.5	c.-7_6dupCAGCATCATGGCG	p.Asp3fs	frameshift_variant	Exon 1 of 1	ENST00000331327.5	NP_005850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PURA	ENST00000331327.5	c.-7_6dupCAGCATCATGGCG	p.Asp3fs	frameshift_variant	Exon 1 of 1	6	NM_005859.5	ENSP00000332706.3
PURA	ENST00000651386.1	c.-7_6dupCAGCATCATGGCG	p.Asp3fs	frameshift_variant	Exon 2 of 2			ENSP00000499133.1
PURA	ENST00000505703.2	c.-7_6dupCAGCATCATGGCG	p.Asp3fs	frameshift_variant	Exon 2 of 2	3		ENSP00000498560.1
PURA	ENST00000502351.1	c.-7_6dupCAGCATCATGGCG	p.Asp3fs	frameshift_variant	Exon 2 of 2	2		ENSP00000498760.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 8

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr5-139493756;