Variant chr5-140114148-AGGCGGCGGCGGCGCGGCAGCGGAGCGCAGCATCATGGCGGACCGAGACAGCGGCAGCGAGCAGGGTGGTGCGGCGCTGGGTTCGGGCGGCTCCCTGGGGCACCCCGGCTCGGGCTCAGGCTCCGGCGGGGGCGGTGGTGGCGGCGGGGGCGGCGGCGGCAGT-A 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.-20_142del variant causes a start lost, 5 prime UTR 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 Pathogenic (★).

Frequency

Genomes: not found (cov: 31)

Consequence

PURA
NM_005859.5 start_lost, 5_prime_UTR

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 3.34

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

Start lost variant, no new inframe start found.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 5-140114148-AGGCGGCGGCGGCGCGGCAGCGGAGCGCAGCATCATGGCGGACCGAGACAGCGGCAGCGAGCAGGGTGGTGCGGCGCTGGGTTCGGGCGGCTCCCTGGGGCACCCCGGCTCGGGCTCAGGCTCCGGCGGGGGCGGTGGTGGCGGCGGGGGCGGCGGCGGCAGT-A is Pathogenic according to our data. Variant chr5-140114148-AGGCGGCGGCGGCGCGGCAGCGGAGCGCAGCATCATGGCGGACCGAGACAGCGGCAGCGAGCAGGGTGGTGCGGCGCTGGGTTCGGGCGGCTCCCTGGGGCACCCCGGCTCGGGCTCAGGCTCCGGCGGGGGCGGTGGTGGCGGCGGGGGCGGCGGCGGCAGT-A is described in ClinVar as [Pathogenic]. Clinvar id is 3149818.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.-20_142del		start_lost, 5_prime_UTR_variant	1/1	ENST00000331327.5

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
PURA	ENST00000331327.5 linkuse as main transcript	c.-20_142del	start_lost, 5_prime_UTR_variant	1/1		NM_005859.5	P1
PURA	ENST00000505703.2 linkuse as main transcript	c.-20_142del	start_lost, 5_prime_UTR_variant	2/2	3
PURA	ENST00000651386.1 linkuse as main transcript	c.-20_142del	start_lost, 5_prime_UTR_variant	2/2			P1
PURA	ENST00000502351.1 linkuse as main transcript		coding_sequence_variant, 5_prime_UTR_variant, 3_prime_UTR_variant	2/2	2

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: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 22, 2023

The c.-20_142del162 (p.M1?) alteration is located in coding exon 1 of the PURA gene and results from a deletion of 162 nucleotides at position -20 to 142. This deletion likely includes the initiation codon. Sequence variations that modify the initiation codon are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This region is not highly conserved in available vertebrate species with limited sequence alignment. Based on the available evidence, this alteration is classified as pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

No publications associated with this variant yet.