16-67174230-G-C

Variant names:

• chr16-67174230-G-C
• rs397514600
• NM_001276309.3:c.61G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001276309.3(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. 13/21 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 NM_001276309.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:1
• Conservation: PhyloP100: 2.74
• Publications: 5 publications found

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]

NOL3 Gene-Disease associations (from GenCC):

• myoclonus, familial

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• myoclonus, familial, 1

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19648546).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001276309.3. 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
	NOL3	NM_001276309.3	MANE Select	c.61G>C	p.Glu21Gln	missense	Exon 2 of 4	NP_001263238.1	Q5TZN6
	NOL3	NM_001394979.1		c.61G>C	p.Glu21Gln	missense	Exon 2 of 4	NP_001381908.1
	NOL3	NM_001185057.3		c.61G>C	p.Glu21Gln	missense	Exon 2 of 4	NP_001171986.1	O60936-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOL3	ENST00000564992.2	TSL:2 MANE Select	c.61G>C	p.Glu21Gln	missense	Exon 2 of 4	ENSP00000457720.2	H3BUN4
	NOL3	ENST00000568146.1	TSL:1	c.61G>C	p.Glu21Gln	missense	Exon 2 of 4	ENSP00000454598.1	O60936-1
	NOL3	ENST00000566871.5	TSL:2	c.163G>C	p.Glu55Gln	missense	Exon 2 of 4	ENSP00000455808.1	H3BQJ5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	1	-	Myoclonus, familial, 1 (2)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.7
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.040
Sift	Benign	0.061	T
Sift4G	Benign	0.47	T
Polyphen		0.43	B
Vest4		0.34
MutPred		0.43		Gain of MoRF binding (P = 0.0428)
MVP		0.47
MPC		1.0
ClinPred		0.45	T
GERP RS		2.9
PromoterAI		-0.051	Neutral
Varity_R		0.38
Mutation Taster		=8/92	disease causing (ClinVar)

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: rs397514600; hg19: chr16-67208133;