5-171410539-C-CTCTG
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPP5_Moderate
The NM_002520.7(NPM1):c.860_863dup(p.Trp288CysfsTer12) variant causes a frameshift change. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 33)
Exomes 𝑓: 7.1e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NPM1
NM_002520.7 frameshift
NM_002520.7 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.84
Genes affected
NPM1 (HGNC:7910): (nucleophosmin 1) The protein encoded by this gene is involved in several cellular processes, including centrosome duplication, protein chaperoning, and cell proliferation. The encoded phosphoprotein shuttles between the nucleolus, nucleus, and cytoplasm, chaperoning ribosomal proteins and core histones from the nucleus to the cytoplasm. This protein is also known to sequester the tumor suppressor ARF in the nucleolus, protecting it from degradation until it is needed. Mutations in this gene are associated with acute myeloid leukemia. Dozens of pseudogenes of this gene have been identified. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 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 12 pathogenic variants in the truncated region.
PP5
Variant 5-171410539-C-CTCTG is Pathogenic according to our data. Variant chr5-171410539-C-CTCTG is described in ClinVar as [Pathogenic]. Clinvar id is 13998.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPM1 | NM_002520.7 | c.860_863dup | p.Trp288CysfsTer12 | frameshift_variant | 11/11 | ENST00000296930.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPM1 | ENST00000296930.10 | c.860_863dup | p.Trp288CysfsTer12 | frameshift_variant | 11/11 | 1 | NM_002520.7 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 150500Hom.: 0 Cov.: 33 FAILED QC
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.14e-7 AC: 1AN: 1400864Hom.: 0 Cov.: 26 AF XY: 0.00000143 AC XY: 1AN XY: 697832
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GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 150500Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 73268
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Acute myeloid leukemia Pathogenic:2
Pathogenic, no assertion criteria provided | research | NIHR Bioresource Rare Diseases, University of Cambridge | - | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 20, 2005 | - - |
Myelodysplastic syndrome progressed to acute myeloid leukemia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Hospital of the University of Pennsylvania, Center for Personalized Diagnostics | Jan 08, 2016 | Usually associated with favorable prognosis in AML unless a concomitant FLT3-ITD mutation is also present - |
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at