rs397514600

Positions:

• chr16-67174230-G-A
• chr16-67174230-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000568146.1(NOL3):​c.61G>A​(p.Glu21Lys) 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. 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. E21Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NOL3 ENST00000568146.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74

Genes affected

NOL3 (HGNC:7869): (nucleolar protein 3) This gene encodes an anti-apoptotic protein that has been shown to down-regulate the enzyme activities of caspase 2, caspase 8 and tumor protein p53. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23320672).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOL3	NM_001276309.3	c.61G>A	p.Glu21Lys	missense_variant	2/4	ENST00000564992.2
NOL3	XM_047434851.1	c.247G>A	p.Glu83Lys	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOL3	ENST00000564992.2	c.61G>A	p.Glu21Lys	missense_variant	2/4	2	NM_001276309.3	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	T;T;T;.;.;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.25	N
LIST_S2	Uncertain	0.93	D;D;D;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.23	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	.;.;L;.;.;L
MutationTaster	Benign	0.94	N;N;N;N
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.3	N;N;N;N;N;N
REVEL	Benign	0.048
Sift	Benign	0.044	D;T;T;.;.;D
Sift4G	Uncertain	0.024	D;D;D;D;D;D
Polyphen		0.37	.;.;B;.;.;.
Vest4		0.46, 0.46, 0.50
MutPred		0.53		Gain of MoRF binding (P = 0.0026);Gain of MoRF binding (P = 0.0026);Gain of MoRF binding (P = 0.0026);Gain of MoRF binding (P = 0.0026);.;Gain of MoRF binding (P = 0.0026);
MVP		0.44
MPC		1.3
ClinPred		0.67	D
GERP RS		2.9
Varity_R		0.24

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

Other links and lift over

dbSNP: rs397514600; hg19: chr16-67208133;