chr16-67174030-C-T

Variant names:

• chr16-67174030-C-T
• rs2233455
• ENST00000568146.1:c.-25C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000568146.1(NOL3):​c.-25C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0808 in 1,549,782 control chromosomes in the GnomAD database, including 7,362 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.13 (2192 hom., cov: 32)
  • Exomes 𝑓: 0.075 (5170 hom.)
• Consequence: NOL3 ENST00000568146.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.657
• Publications: 35 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 16-67174030-C-T is Benign according to our data. Variant chr16-67174030-C-T is described in ClinVar as Benign. ClinVar VariationId is 3055509.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOL3	NM_001185057.3	c.-25C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4		NP_001171986.1
NOL3	NM_001394978.1	c.-25C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 5		NP_001381907.1
NOL3	NM_001276307.3	c.-25C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 3 of 6		NP_001263236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOL3	ENST00000564992.2	c.-8-132C>T		intron_variant	Intron 1 of 3	2		ENSP00000457720.2

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20377 AN: 152056 Hom.: 2184 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0753

Gnomad ASJ AF: 0.0302

Gnomad EAS AF: 0.0181

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0667

Gnomad OTH AF: 0.103

GnomAD2 exomes AF: 0.0845 AC: 12660 AN: 149896 AF XY: 0.0829

Gnomad AFR exome AF: 0.304

Gnomad AMR exome AF: 0.0700

Gnomad ASJ exome AF: 0.0341

Gnomad EAS exome AF: 0.0150

Gnomad FIN exome AF: 0.116

Gnomad NFE exome AF: 0.0684

Gnomad OTH exome AF: 0.0614

GnomAD4 exome AF: 0.0750 AC: 104763 AN: 1397608 Hom.: 5170 Cov.: 33 AF XY: 0.0750 AC XY: 51728 AN XY: 689900

African (AFR) AF: 0.299 AC: 9506 AN: 31790

American (AMR) AF: 0.0705 AC: 2528 AN: 35862

Ashkenazi Jewish (ASJ) AF: 0.0348 AC: 877 AN: 25180

East Asian (EAS) AF: 0.0178 AC: 641 AN: 35918

South Asian (SAS) AF: 0.108 AC: 8624 AN: 79868

European-Finnish (FIN) AF: 0.113 AC: 5110 AN: 45148

Middle Eastern (MID) AF: 0.0544 AC: 310 AN: 5696

European-Non Finnish (NFE) AF: 0.0673 AC: 72657 AN: 1080064

Other (OTH) AF: 0.0776 AC: 4510 AN: 58082

GnomAD4 genome AF: 0.134 AC: 20421 AN: 152174 Hom.: 2192 Cov.: 32 AF XY: 0.135 AC XY: 10045 AN XY: 74410

African (AFR) AF: 0.298 AC: 12346 AN: 41486

American (AMR) AF: 0.0754 AC: 1154 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0302 AC: 105 AN: 3472

East Asian (EAS) AF: 0.0182 AC: 94 AN: 5174

South Asian (SAS) AF: 0.111 AC: 537 AN: 4828

European-Finnish (FIN) AF: 0.123 AC: 1306 AN: 10586

Middle Eastern (MID) AF: 0.0582 AC: 17 AN: 292

European-Non Finnish (NFE) AF: 0.0667 AC: 4539 AN: 68014

Other (OTH) AF: 0.103 AC: 218 AN: 2110

Alfa AF: 0.0817 Hom.: 1257

Bravo AF: 0.137

Asia WGS AF: 0.0980 AC: 343 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

NOL3-related disorder Benign:1

Sep 06, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.5
DANN	Benign	0.68
PhyloP100		-0.66
PromoterAI		-0.067	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs2233455; hg19: chr16-67207933; COSMIC: COSV50456982; COSMIC: COSV50456982;