chr16-28538023-C-T

Variant names:

• chr16-28538023-C-T
• rs776052143
• NM_012385.3:c.245G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012385.3(NUPR1):​c.245G>A​(p.Arg82His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,612,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R82C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: NUPR1 NM_012385.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.65
• Publications: 2 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13363338).

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.245G>A	p.Arg82His	missense	Exon 2 of 3	NP_036517.1	O60356-1
	NUPR1	NM_001042483.2		c.299G>A	p.Arg100His	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.245G>A	p.Arg82His	missense	Exon 2 of 3	ENSP00000315559.7	O60356-1
	NUPR1	ENST00000876798.1		c.326G>A	p.Arg109His	missense	Exon 3 of 4	ENSP00000546857.1
	NUPR1	ENST00000395641.2	TSL:2	c.299G>A	p.Arg100His	missense	Exon 2 of 3	ENSP00000379003.2	O60356-2

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

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: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250462 AF XY: 0.00

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: 0.0000468

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000301 AC: 44 AN: 1460428 Hom.: 0 Cov.: 31 AF XY: 0.0000358 AC XY: 26 AN XY: 726392

African (AFR) AF: 0.000149 AC: 5 AN: 33466

American (AMR) AF: 0.0000224 AC: 1 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86156

European-Finnish (FIN) AF: 0.000113 AC: 6 AN: 52996

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.0000234 AC: 26 AN: 1111256

Other (OTH) AF: 0.0000497 AC: 3 AN: 60366

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74484

African (AFR) AF: 0.0000962 AC: 4 AN: 41562

American (AMR) AF: 0.00 AC: 0 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000264

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	Benign	0.15
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.6
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.047
Sift	Benign	0.14	T
Sift4G	Uncertain	0.027	D
Polyphen		0.80	P
Vest4		0.13
MVP		0.42
MPC		0.36
ClinPred		0.86	D
GERP RS		1.3
Varity_R		0.031
gMVP		0.10
Mutation Taster		=94/6	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: rs776052143; hg19: chr16-28549344;