chr16-28538843-G-A

Variant names:

• chr16-28538843-G-A
• rs1340715161
• NM_012385.3:c.65C>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.65C>T​(p.Ser22Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. 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. S22C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUPR1 NM_012385.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56
• 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: 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=0.05536911).

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.65C>T	p.Ser22Phe	missense	Exon 1 of 3	NP_036517.1	O60356-1
	NUPR1	NM_001042483.2		c.65C>T	p.Ser22Phe	missense	Exon 1 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.65C>T	p.Ser22Phe	missense	Exon 1 of 3	ENSP00000315559.7	O60356-1
	NUPR1	ENST00000876798.1		c.65C>T	p.Ser22Phe	missense	Exon 1 of 4	ENSP00000546857.1
	NUPR1	ENST00000395641.2	TSL:2	c.65C>T	p.Ser22Phe	missense	Exon 1 of 3	ENSP00000379003.2	O60356-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.33
DANN	Benign	0.96
DEOGEN2	Benign	0.21	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
PhyloP100		-2.6
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.043
Sift	Benign	0.044	D
Sift4G	Benign	0.16	T
Polyphen		0.0070	B
Vest4		0.091
MutPred		0.30		Loss of phosphorylation at S22 (P = 0.0059)
MVP		0.081
MPC		0.090
ClinPred		0.53	D
GERP RS		-9.1
PromoterAI		0.032	Neutral
Varity_R		0.060
gMVP		0.072

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: rs1340715161; hg19: chr16-28550164; COSMIC: COSV100257250;