16-67174230-G-C

Position:

• chr16-67174230-G-C

Variant summary

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

The ENST00000564992.2(NOL3):​c.61G>C​(p.Glu21Gln) 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NOL3 ENST00000564992.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:1
• 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=0.19648546).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOL3	NM_001276309.3	c.61G>C	p.Glu21Gln	missense_variant	2/4	ENST00000564992.2	NP_001263238.1
NOL3	XM_047434851.1	c.247G>C	p.Glu83Gln	missense_variant	3/5		XP_047290807.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOL3	ENST00000564992.2	c.61G>C	p.Glu21Gln	missense_variant	2/4	2	NM_001276309.3	ENSP00000457720	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1 Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Myoclonus, familial, 1 Pathogenic:1 Uncertain:1

Uncertain significance, criteria provided, single submitter	clinical testing	Revvity Omics, Revvity	Apr 01, 2020	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Aug 01, 2012	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T;T;T;.;.;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.82	T;T;T;T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.20	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	.;.;N;.;.;N
MutationTaster	Benign	0.99	N;N;N;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.8	N;N;N;N;N;N
REVEL	Benign	0.040
Sift	Benign	0.061	T;T;D;.;.;D
Sift4G	Benign	0.47	T;T;T;T;T;T
Polyphen		0.43	.;.;B;.;.;.
Vest4		0.34, 0.35, 0.38
MutPred		0.43		Gain of MoRF binding (P = 0.0428);Gain of MoRF binding (P = 0.0428);Gain of MoRF binding (P = 0.0428);Gain of MoRF binding (P = 0.0428);.;Gain of MoRF binding (P = 0.0428);
MVP		0.47
MPC		1.0
ClinPred		0.45	T
GERP RS		2.9
Varity_R		0.38

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;