chr5-171392949-C-T
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_002520.7(NPM1):c.495C>T(p.Asp165=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000634 in 1,607,674 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0031 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00037 ( 5 hom. )
Consequence
NPM1
NM_002520.7 synonymous
NM_002520.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.90
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 Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
Variant 5-171392949-C-T is Benign according to our data. Variant chr5-171392949-C-T is described in ClinVar as [Benign]. Clinvar id is 730555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.9 with no splicing effect.
BS2
?
High AC in GnomAd at 474 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPM1 | NM_002520.7 | c.495C>T | p.Asp165= | synonymous_variant | 6/11 | ENST00000296930.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPM1 | ENST00000296930.10 | c.495C>T | p.Asp165= | synonymous_variant | 6/11 | 1 | NM_002520.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00312 AC: 474AN: 151768Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.000777 AC: 194AN: 249570Hom.: 1 AF XY: 0.000555 AC XY: 75AN XY: 135162
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GnomAD4 exome AF: 0.000374 AC: 544AN: 1455788Hom.: 5 Cov.: 32 AF XY: 0.000315 AC XY: 228AN XY: 724590
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | May 31, 2018 | - - |
NPM1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 08, 2024 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
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Dann
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RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at