Variant 5-171392949-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002520.7(NPM1):c.495C>G(p.Asp165Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,607,566 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: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NPM1
NM_002520.7 missense

Scores

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]

NPM1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.042381823).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPM1	NM_002520.7 link	c.495C>G	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
NPM1	ENST00000296930.10 link	c.495C>G	p.Asp165Glu	missense_variant	Exon 6 of 11	1	NM_002520.7	ENSP00000296930.5		P06748-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151774

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1455792

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724590

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000271

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151774

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74096

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.039

DANN

Benign

0.90

DEOGEN2

Benign

0.14

T;T;T;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.61

.;T;T;T;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.042

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.56

N;N;.;N;N

PrimateAI

Benign

0.45

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

0.038

GERP RS

-7.5

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over