5-140114183-T-TGGCG

Variant summary

Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1 PS1_Moderate PM2 PP5_Moderate

The NM_005859.5(PURA):c.4_7dup(p.Asp3?) variant causes a frameshift, start lost change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. MADRDSGSEQGGAALGSGGSLGHPGSGSGSGGGGGGGGGGGGSGGGGGGAPGGLQHETQELASKRVDIQNKRFYLDVKQNAKGRFLKI1?) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PURA NM_005859.5 frameshift, start_lost
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 4.44

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 14 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 157 pathogenic variants in the truncated region.
• PS1: Another start lost variant in NM_005859.5 (PURA) was described as [Likely_pathogenic] in ClinVar as 489294
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 5-140114183-T-TGGCG is Pathogenic according to our data. Variant chr5-140114183-T-TGGCG is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2441816.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.4_7dup	p.Asp3?	frameshift_variant, start_lost	1/1	ENST00000331327.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PURA	ENST00000331327.5	c.4_7dup	p.Asp3?	frameshift_variant, start_lost	1/1		NM_005859.5	P1
PURA	ENST00000502351.1	c.4_7dup	p.Asp3?	frameshift_variant, start_lost	2/2	2
PURA	ENST00000505703.2	c.4_7dup	p.Asp3?	frameshift_variant, start_lost	2/2	3
PURA	ENST00000651386.1	c.4_7dup	p.Asp3?	frameshift_variant, start_lost	2/2			P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 9

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Likely pathogenic, criteria provided, single submitter

clinical testing

Baylor Genetics

Oct 13, 2022

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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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-139493768;