chr16-67174230-G-T

Variant names:

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

Variant summary

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

The NM_001276309.3(NOL3):​c.61G>T​(p.Glu21*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NOL3 NM_001276309.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>T	p.Glu21*	stop_gained	Exon 2 of 4	NP_001263238.1	Q5TZN6
	NOL3	NM_001394979.1		c.61G>T	p.Glu21*	stop_gained	Exon 2 of 4	NP_001381908.1
	NOL3	NM_001185057.3		c.61G>T	p.Glu21*	stop_gained	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>T	p.Glu21*	stop_gained	Exon 2 of 4	ENSP00000457720.2	H3BUN4
	NOL3	ENST00000568146.1	TSL:1	c.61G>T	p.Glu21*	stop_gained	Exon 2 of 4	ENSP00000454598.1	O60936-1
	NOL3	ENST00000566871.5	TSL:2	c.163G>T	p.Glu55*	stop_gained	Exon 2 of 4	ENSP00000455808.1	H3BQJ5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460702 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726666

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52560

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111842

Other (OTH) AF: 0.00 AC: 0 AN: 60362

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.40
CADD	Pathogenic	38
DANN	Uncertain	0.99
Eigen	Uncertain	0.41
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.30	N
PhyloP100		2.7
Vest4		0.74
GERP RS		2.9
PromoterAI		0.034	Neutral

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;