chr5-140114183-T-TGGCG

Variant summary

Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1PS1_ModeratePM2PP5_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

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 4.44
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]

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ACMG classification

Classification made for transcript

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 161 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
PURANM_005859.5 linkuse as main transcriptc.4_7dup p.Asp3? frameshift_variant, start_lost 1/1 ENST00000331327.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PURAENST00000331327.5 linkuse as main transcriptc.4_7dup p.Asp3? frameshift_variant, start_lost 1/1 NM_005859.5 P1
PURAENST00000502351.1 linkuse as main transcriptc.4_7dup p.Asp3? frameshift_variant, start_lost 2/22
PURAENST00000505703.2 linkuse as main transcriptc.4_7dup p.Asp3? frameshift_variant, start_lost 2/23
PURAENST00000651386.1 linkuse as main transcriptc.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
LINK: link

Submissions by phenotype

PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitterclinical testingBaylor GeneticsOct 13, 2022- -

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.

Other links and lift over

hg19: chr5-139493768; API