dbSNP rs1302267023: NUPR2:p.Ala5Ala (chr7-56116300-T-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -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 id is 2657517.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUPR2	NM_001145712.2 link	c.15A>T	p.Ala5Ala	synonymous_variant	Exon 1 of 2	ENST00000329309.4	NP_001139184.1	A6NF83

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUPR2	ENST00000329309.4 link	c.15A>T	p.Ala5Ala	synonymous_variant	Exon 1 of 2	1	NM_001145712.2	ENSP00000455442.1		A6NF83

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

GnomAD3 exomes

AF:

0.0000347

AC:

AN:

57698

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

33778

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 SAS exome

AF:

0.0000870

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

Gnomad4 AFR exome

AF:

0.0000478

Gnomad4 AMR exome

AF:

0.000142

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000113

Gnomad4 SAS exome

AF:

0.0000460

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.0000645

GnomAD4 genome

AF:

0.0000350

AC:

AN:

142890

Hom.:

Cov.:

AF XY:

0.0000574

AC XY:

AN XY:

69630

show subpopulations

Gnomad4 AFR

AF:

0.0000777

Gnomad4 AMR

AF:

0.0000694

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000152

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NUPR2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

4.1

DANN

Benign

0.54

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over