Genetic Variant NUPR2:p.Glu6Lys (chr7-56116299-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145712.2(NUPR2):c.16G>A(p.Glu6Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E6V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NUPR2
NM_001145712.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.20

Publications

0 publications found

Variant links:

Genes affected

NUPR2 (HGNC:44164): (nuclear protein 2, transcriptional regulator) Involved in several processes, including cellular response to starvation; negative regulation of cell population proliferation; and negative regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

NUPR2 links:

ENSG00000308815 (HGNC:):

ENSG00000308815 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055039585).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145712.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUPR2	NM_001145712.2	MANE Select	c.16G>A	p.Glu6Lys	missense	Exon 1 of 2	NP_001139184.1	A6NF83

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NUPR2	ENST00000329309.4	TSL:1 MANE Select	c.16G>A	p.Glu6Lys	missense	Exon 1 of 2	ENSP00000455442.1	A6NF83
ENSG00000308815	ENST00000836569.1		n.-207C>T		upstream_gene	N/A
ENSG00000308815	ENST00000836570.1		n.-207C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151816

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

60048

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1301086

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

640506

African (AFR)

AF:

0.00

AC:

AN:

24366

American (AMR)

AF:

0.00

AC:

AN:

16020

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20438

East Asian (EAS)

AF:

0.00

AC:

AN:

30566

South Asian (SAS)

AF:

0.00

AC:

AN:

67454

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44716

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3890

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1040566

Other (OTH)

AF:

0.00

AC:

AN:

53070

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151926

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41498

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5100

South Asian (SAS)

AF:

0.00

AC:

AN:

4784

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67906

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.63

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.011

FATHMM_MKL

Benign

0.0060

LIST_S2

Benign

0.37

M_CAP

Benign

0.0033

MetaRNN

Benign

0.055

PhyloP100

-1.2

PrimateAI

Uncertain

0.69

PROVEAN

Benign

0.080

Sift

Pathogenic

0.0

Sift4G

Benign

0.30

Polyphen

0.0

Vest4

0.052

MVP

0.014

GERP RS

-1.1

PromoterAI

-0.011

Neutral

(source)

Varity_R

0.050

gMVP

0.18

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over