7-56116300-T-G

Variant names:

• chr7-56116300-T-G
• rs1302267023
• NM_001145712.2:c.15A>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001145712.2(NUPR2):​c.15A>C​(p.Ala5Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,169,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A5A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: NUPR2 NM_001145712.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16
• Publications: 0 publications found

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]

ENSG00000308815 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• 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>C	p.Ala5Ala	synonymous	Exon 1 of 2	NP_001139184.1	A6NF83

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUPR2	ENST00000329309.4	TSL:1 MANE Select	c.15A>C	p.Ala5Ala	synonymous	Exon 1 of 2	ENSP00000455442.1	A6NF83
	ENSG00000308815	ENST00000836569.1		n.-206T>G		upstream_gene	N/A
	ENSG00000308815	ENST00000836570.1		n.-206T>G		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.000100 AC: 117 AN: 1169038 Hom.: 0 Cov.: 30 AF XY: 0.0000916 AC XY: 53 AN XY: 578292

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000478 AC: 1 AN: 20926

American (AMR) AF: 0.000496 AC: 7 AN: 14100

Ashkenazi Jewish (ASJ) AF: 0.000230 AC: 4 AN: 17386

East Asian (EAS) AF: 0.000492 AC: 13 AN: 26444

South Asian (SAS) AF: 0.0000153 AC: 1 AN: 65236

European-Finnish (FIN) AF: 0.000617 AC: 23 AN: 37294

Middle Eastern (MID) AF: 0.000294 AC: 1 AN: 3400

European-Non Finnish (NFE) AF: 0.0000629 AC: 59 AN: 937746

Other (OTH) AF: 0.000172 AC: 8 AN: 46506

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.2
DANN	Benign	0.37
PhyloP100		-2.2
PromoterAI		0.036	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1302267023; hg19: chr7-56183993;