chr5-171392976-A-T

Variant names:

• chr5-171392976-A-T
• NM_002520.7:c.522A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002520.7(NPM1):​c.522A>T​(p.Glu174Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NPM1 NM_002520.7 missense, splice_region
• Scores: Splicing: ADA: 0.001588
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.949

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.085398346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPM1	NM_002520.7	c.522A>T	p.Glu174Asp	missense_variant, splice_region_variant	Exon 6 of 11	ENST00000296930.10	NP_002511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPM1	ENST00000296930.10	c.522A>T	p.Glu174Asp	missense_variant, splice_region_variant	Exon 6 of 11	1	NM_002520.7	ENSP00000296930.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	15
DANN	Benign	0.78
DEOGEN2	Benign	0.10	T;T;T;.;.
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.60
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.55	.;T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.085	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.060	N;N;.;N;N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.050	N;N;N;N;N
REVEL	Benign	0.20
Sift	Benign	1.0	T;T;D;T;T
Sift4G	Benign	0.62	T;T;T;T;T
Polyphen		0.0	B;B;.;B;.
Vest4		0.35
MutPred		0.37		Loss of stability (P = 0.1688);Loss of stability (P = 0.1688);.;Loss of stability (P = 0.1688);Loss of stability (P = 0.1688);
MVP		0.72
MPC		0.17
ClinPred		0.10	T
GERP RS		2.5
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		3.8
Varity_R		0.060
gMVP		0.014

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0016
dbscSNV1_RF	Benign	0.076
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-170819980;