rs8057598

Positions:

• chr16-67175352-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000568146.1(NOL3):​c.*255A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,293,680 control chromosomes in the GnomAD database, including 16,053 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (7602 hom., cov: 33)
  • Exomes 𝑓: 0.085 (8451 hom.)
• Consequence: NOL3 ENST00000568146.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOL3	NM_001276309.3	c.*298A>G		3_prime_UTR_variant	4/4	ENST00000564992.2
NOL3	XM_047434851.1	c.*298A>G		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOL3	ENST00000564992.2	c.*298A>G		3_prime_UTR_variant	4/4	2	NM_001276309.3	P2

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33481 AN: 152002 Hom.: 7567 Cov.: 33

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.0216

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0691

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.0851 AC: 97157 AN: 1141560 Hom.: 8451 Cov.: 30 AF XY: 0.0851 AC XY: 46284 AN XY: 544184

Gnomad4 AFR exome AF: 0.616

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.0398

Gnomad4 EAS exome AF: 0.0194

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.0686

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.221 AC: 33576 AN: 152120 Hom.: 7602 Cov.: 33 AF XY: 0.219 AC XY: 16317 AN XY: 74374

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.0343

Gnomad4 EAS AF: 0.0216

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.0691

Gnomad4 OTH AF: 0.163

Alfa AF: 0.0967 Hom.: 1336

Bravo AF: 0.233

Asia WGS AF: 0.151 AC: 525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.7
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs8057598; hg19: chr16-67209255;