16-28538048-C-T

Variant names:

• chr16-28538048-C-T
• rs200282077
• NM_012385.3:c.220G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012385.3(NUPR1):​c.220G>A​(p.Glu74Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000421 in 1,614,018 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: NUPR1 NM_012385.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.71
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012385.3. 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.220G>A	p.Glu74Lys	missense	Exon 2 of 3	NP_036517.1	O60356-1
	NUPR1	NM_001042483.2		c.274G>A	p.Glu92Lys	missense	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.220G>A	p.Glu74Lys	missense	Exon 2 of 3	ENSP00000315559.7	O60356-1
	NUPR1	ENST00000876798.1		c.301G>A	p.Glu101Lys	missense	Exon 3 of 4	ENSP00000546857.1
	NUPR1	ENST00000395641.2	TSL:2	c.274G>A	p.Glu92Lys	missense	Exon 2 of 3	ENSP00000379003.2	O60356-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251294 AF XY: 0.0000221

Gnomad AFR exome AF: 0.000123

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: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000458 AC: 67 AN: 1461796 Hom.: 0 Cov.: 31 AF XY: 0.0000358 AC XY: 26 AN XY: 727198

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000585 AC: 65 AN: 1111976

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152222 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74374

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000386 Hom.: 0

Bravo AF: 0.0000227

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.63	D
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Uncertain	-0.11	T
PhyloP100		4.7
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.25
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.69
MVP		0.39
MPC		0.25
ClinPred		0.93	D
GERP RS		5.4
Varity_R		0.48
gMVP		0.52
Mutation Taster		=76/24	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: rs200282077; hg19: chr16-28549369;