16-28538081-C-G

Variant names:

• chr16-28538081-C-G
• rs371618392
• NM_012385.3:c.187G>C

Variant summary

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

The NM_012385.3(NUPR1):​c.187G>C​(p.Glu63Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000109 in 1,461,864 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E63K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (1 hom.)
• Consequence: NUPR1 NM_012385.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.71
• Publications: 3 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 0 ACMG points.

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.187G>C	p.Glu63Gln	missense	Exon 2 of 3	NP_036517.1	O60356-1
	NUPR1	NM_001042483.2		c.241G>C	p.Glu81Gln	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.187G>C	p.Glu63Gln	missense	Exon 2 of 3	ENSP00000315559.7	O60356-1
	NUPR1	ENST00000876798.1		c.268G>C	p.Glu90Gln	missense	Exon 3 of 4	ENSP00000546857.1
	NUPR1	ENST00000395641.2	TSL:2	c.241G>C	p.Glu81Gln	missense	Exon 2 of 3	ENSP00000379003.2	O60356-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000318 AC: 8 AN: 251314 AF XY: 0.0000442

Gnomad AFR exome AF: 0.00

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: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461864 Hom.: 1 Cov.: 31 AF XY: 0.0000193 AC XY: 14 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112008

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

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000330 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Uncertain	-0.13	T
PhyloP100		4.7
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.12
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.67
MutPred		0.36		Gain of MoRF binding (P = 0.0522)
MVP		0.39
MPC		0.33
ClinPred		0.90	D
GERP RS		5.5
Varity_R		0.28
gMVP		0.38
Mutation Taster		=82/18	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: rs371618392; hg19: chr16-28549402; COSMIC: COSV61405145;