rs146936311

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002520.7(NPM1):​c.495C>A​(p.Asp165Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,455,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

NPM1
NM_002520.7 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.90
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.043557793).
BS2
High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NPM1NM_002520.7 linkc.495C>A p.Asp165Glu missense_variant Exon 6 of 11 ENST00000296930.10 NP_002511.1 P06748-1A0A0S2Z491

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NPM1ENST00000296930.10 linkc.495C>A p.Asp165Glu missense_variant Exon 6 of 11 1 NM_002520.7 ENSP00000296930.5 P06748-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249570
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135162
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000481
AC:
7
AN:
1455792
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
724590
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000452
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.082
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
0.024
DANN
Benign
0.89
DEOGEN2
Benign
0.14
T;T;T;.;.
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.070
N
LIST_S2
Benign
0.61
.;T;T;T;T
M_CAP
Benign
0.0039
T
MetaRNN
Benign
0.044
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.56
N;N;.;N;N
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-1.0
N;N;N;N;N
REVEL
Benign
0.046
Sift
Benign
0.14
T;T;T;T;T
Sift4G
Benign
0.38
T;T;T;T;T
Polyphen
0.0070
B;B;.;B;.
Vest4
0.24
MutPred
0.35
Loss of stability (P = 0.1227);Loss of stability (P = 0.1227);.;Loss of stability (P = 0.1227);Loss of stability (P = 0.1227);
MVP
0.37
MPC
0.17
ClinPred
0.034
T
GERP RS
-7.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.067
gMVP
0.0074

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs146936311; hg19: chr5-170819953; API