NM_012385.3:c.113-16C>T

Variant names:

• chr16-28538171-G-A
• rs777281941
• NM_012385.3:c.113-16C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012385.3(NUPR1):​c.113-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: NUPR1 NM_012385.3 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0630
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0628449).

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.113-16C>T		intron	N/A	NP_036517.1	O60356-1
	NUPR1	NM_001042483.2		c.151C>T	p.Pro51Ser	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.113-16C>T		intron	N/A	ENSP00000315559.7	O60356-1
	NUPR1	ENST00000395641.2	TSL:2	c.151C>T	p.Pro51Ser	missense	Exon 2 of 3	ENSP00000379003.2	O60356-2
	NUPR1	ENST00000876798.1		c.194-16C>T		intron	N/A	ENSP00000546857.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 250794 AF XY: 0.0000221

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.0000289

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: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461824 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727212

African (AFR) AF: 0.000209 AC: 7 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

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: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111988

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152208 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74368

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000169 AC: 7 AN: 41448

American (AMR) AF: 0.0000655 AC: 1 AN: 15276

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00303499), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.0000567

ExAC AF: 0.00000824 AC: 1

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	0.080
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.8
DANN	Benign	0.56
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.063
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.32	N
REVEL	Benign	0.0040
Sift	Benign	0.47	T
Sift4G	Benign	0.29	T
Vest4		0.036
MVP		0.095
MPC		0.36
ClinPred		0.017	T
GERP RS		-3.3
gMVP		0.12

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: rs777281941; hg19: chr16-28549492;