16-28538081-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012385.3(NUPR1):​c.187G>A​(p.Glu63Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000102 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

NUPR1
NM_012385.3 missense

Scores

6
9
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.71
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NUPR1NM_012385.3 linkc.187G>A p.Glu63Lys missense_variant Exon 2 of 3 ENST00000324873.8 NP_036517.1 O60356-1A0A024QZC4
NUPR1NM_001042483.2 linkc.241G>A p.Glu81Lys missense_variant Exon 2 of 3 NP_001035948.1 O60356-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NUPR1ENST00000324873.8 linkc.187G>A p.Glu63Lys missense_variant Exon 2 of 3 1 NM_012385.3 ENSP00000315559.7 O60356-1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152216
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000995
AC:
25
AN:
251314
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135834
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000260
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000272
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000107
AC:
157
AN:
1461862
Hom.:
0
Cov.:
31
AF XY:
0.0000935
AC XY:
68
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000120
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152216
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000494
Hom.:
0
Bravo
AF:
0.0000718
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 30, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.241G>A (p.E81K) alteration is located in exon 2 (coding exon 2) of the NUPR1 gene. This alteration results from a G to A substitution at nucleotide position 241, causing the glutamic acid (E) at amino acid position 81 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.66
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Pathogenic
0.34
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.62
D;.
Eigen
Pathogenic
0.71
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Benign
0.025
T
MetaRNN
Uncertain
0.63
D;D
MetaSVM
Uncertain
-0.12
T
PrimateAI
Uncertain
0.74
T
PROVEAN
Uncertain
-2.7
D;N
REVEL
Benign
0.21
Sift
Uncertain
0.010
D;D
Sift4G
Uncertain
0.010
D;D
Polyphen
1.0
D;.
Vest4
0.81
MVP
0.36
MPC
0.25
ClinPred
0.62
D
GERP RS
5.5
Varity_R
0.41
gMVP
0.52

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs371618392; hg19: chr16-28549402; API