chr5-171392719-A-G

Position:

• chr5-171392719-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002520.7(NPM1):​c.362A>G​(p.Glu121Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: NPM1 NM_002520.7 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 5.79

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPM1	NM_002520.7	c.362A>G	p.Glu121Gly	missense_variant	5/11	ENST00000296930.10	NP_002511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPM1	ENST00000296930.10	c.362A>G	p.Glu121Gly	missense_variant	5/11	1	NM_002520.7	ENSP00000296930	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;T;T;.;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.79	.;T;T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.63	D;D;D;D;D
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.6	M;M;.;M;M
MutationTaster	Benign	0.77	N;N;N;N
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.6	D;D;D;D;D
REVEL	Benign	0.26
Sift	Benign	0.24	T;T;T;T;T
Sift4G	Benign	0.062	T;T;T;T;T
Polyphen		0.76	P;P;.;D;.
Vest4		0.41
MutPred		0.76		Loss of stability (P = 0.0251);Loss of stability (P = 0.0251);.;Loss of stability (P = 0.0251);Loss of stability (P = 0.0251);
MVP		0.49
MPC		2.8
ClinPred		0.98	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.20
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs587778580; hg19: chr5-170819723;