Genetic Variant NUPR2:p.Ala5Ala (chr7-56116300-T-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001145712.2(NUPR2):c.15A>T(p.Ala5Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000035 in 142,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000035 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000033 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NUPR2
NM_001145712.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.16

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 7-56116300-T-A is Benign according to our data. Variant chr7-56116300-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2657517.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.16 with no splicing effect.

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.15A>T	p.Ala5Ala	synonymous	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.15A>T	p.Ala5Ala	synonymous	Exon 1 of 2	ENSP00000455442.1	A6NF83
ENSG00000308815	ENST00000836569.1		n.-206T>A		upstream_gene	N/A
ENSG00000308815	ENST00000836570.1		n.-206T>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000350

AC:

AN:

142738

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000780

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000695

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:

0.0000152

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000347

AC:

AN:

57698

AF XY:

0.0000296

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000370

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: AS_VQSR

AF:

0.0000334

AC:

AN:

1168734

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

578142

show subpopulations

African (AFR)

AF:

0.0000478

AC:

AN:

20918

American (AMR)

AF:

0.000142

AC:

AN:

14100

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17386

East Asian (EAS)

AF:

0.000113

AC:

AN:

26454

South Asian (SAS)

AF:

0.0000460

AC:

AN:

65224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37300

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3398

European-Non Finnish (NFE)

AF:

0.0000288

AC:

AN:

937456

Other (OTH)

AF:

0.0000645

AC:

AN:

46498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000350

AC:

AN:

142890

Hom.:

Cov.:

AF XY:

0.0000574

AC XY:

AN XY:

69630

show subpopulations

African (AFR)

AF:

0.0000777

AC:

AN:

38590

American (AMR)

AF:

0.0000694

AC:

AN:

14410

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3388

East Asian (EAS)

AF:

0.00

AC:

AN:

4028

South Asian (SAS)

AF:

0.00

AC:

AN:

3874

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9464

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000152

AC:

AN:

65924

Other (OTH)

AF:

0.00

AC:

AN:

2042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

4.1

(source)

DANN

Benign

0.54

PhyloP100

-2.2

PromoterAI

0.026

Neutral

(source)

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over