rs151227

Variant names:

• chr16-28538187-G-A
• rs151227
• NM_012385.3:c.113-32C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001042483.2(NUPR1):​c.135C>T​(p.Pro45Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,613,596 control chromosomes in the GnomAD database, including 11,531 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (970 hom., cov: 31)
  • Exomes 𝑓: 0.12 (10561 hom.)
• Consequence: NUPR1 NM_001042483.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.399
• Publications: 24 publications found

Genes affected

NUPR1 (HGNC:29990): (nuclear protein 1, transcriptional regulator) Enables DNA binding activity and transcription coactivator activity. Involved in several processes, including regulation of cellular catabolic process; regulation of generation of precursor metabolites and energy; and regulation of programmed cell death. Acts upstream of or within negative regulation of cell cycle. Located in intercellular bridge; nucleoplasm; and perinuclear region of cytoplasm. Part of protein-DNA complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000289754 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=0.399 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042483.2. 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
	NUPR1	NM_012385.3	MANE Select	c.113-32C>T		intron	N/A	NP_036517.1	O60356-1
	NUPR1	NM_001042483.2		c.135C>T	p.Pro45Pro	synonymous	Exon 2 of 3	NP_001035948.1	O60356-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUPR1	ENST00000324873.8	TSL:1 MANE Select	c.113-32C>T		intron	N/A	ENSP00000315559.7	O60356-1
	NUPR1	ENST00000395641.2	TSL:2	c.135C>T	p.Pro45Pro	synonymous	Exon 2 of 3	ENSP00000379003.2	O60356-2
	NUPR1	ENST00000876798.1		c.194-32C>T		intron	N/A	ENSP00000546857.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16339 AN: 151986 Hom.: 970 Cov.: 31

Gnomad AFR AF: 0.0860

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0979

Gnomad FIN AF: 0.0908

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.133

GnomAD2 exomes AF: 0.100 AC: 25064 AN: 250438 AF XY: 0.103

Gnomad AFR exome AF: 0.0853

Gnomad AMR exome AF: 0.0672

Gnomad ASJ exome AF: 0.168

Gnomad EAS exome AF: 0.000816

Gnomad FIN exome AF: 0.0894

Gnomad NFE exome AF: 0.124

Gnomad OTH exome AF: 0.116

GnomAD4 exome AF: 0.117 AC: 170451 AN: 1461492 Hom.: 10561 Cov.: 32 AF XY: 0.117 AC XY: 84745 AN XY: 727056

African (AFR) AF: 0.0891 AC: 2982 AN: 33478

American (AMR) AF: 0.0697 AC: 3115 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 4348 AN: 26132

East Asian (EAS) AF: 0.000554 AC: 22 AN: 39690

South Asian (SAS) AF: 0.0986 AC: 8504 AN: 86250

European-Finnish (FIN) AF: 0.0873 AC: 4656 AN: 53352

Middle Eastern (MID) AF: 0.178 AC: 1024 AN: 5768

European-Non Finnish (NFE) AF: 0.125 AC: 138551 AN: 1111716

Other (OTH) AF: 0.120 AC: 7249 AN: 60386

GnomAD4 genome AF: 0.107 AC: 16339 AN: 152104 Hom.: 970 Cov.: 31 AF XY: 0.105 AC XY: 7833 AN XY: 74350

African (AFR) AF: 0.0858 AC: 3560 AN: 41506

American (AMR) AF: 0.113 AC: 1719 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 582 AN: 3468

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5174

South Asian (SAS) AF: 0.0984 AC: 473 AN: 4808

European-Finnish (FIN) AF: 0.0908 AC: 962 AN: 10598

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8463 AN: 67970

Other (OTH) AF: 0.132 AC: 278 AN: 2110

Alfa AF: 0.119 Hom.: 2046

Bravo AF: 0.109

Asia WGS AF: 0.0500 AC: 173 AN: 3478

EpiCase AF: 0.137

EpiControl AF: 0.135

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.1
DANN	Benign	0.45
PhyloP100		0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.4
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs151227; hg19: chr16-28549508; COSMIC: COSV61404853;