Variant 16-67174667-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The ENST00000564992.2(NOL3):c.342G>C(p.Thr114=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000749 in 1,583,416 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00077 ( 1 hom. )

Consequence

NOL3
ENST00000564992.2 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.0190

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028761).

BP6

Variant 16-67174667-G-C is Benign according to our data. Variant chr16-67174667-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 710884.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}. Variant chr16-67174667-G-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.019 with no splicing effect.

BS2

High AC in GnomAd4 at 89 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOL3	NM_001276309.3 linkuse as main transcript	c.342G>C	p.Thr114=	synonymous_variant	3/4	ENST00000564992.2	NP_001263238.1
NOL3	XM_047434851.1 linkuse as main transcript	c.528G>C	p.Thr176=	synonymous_variant	4/5		XP_047290807.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOL3	ENST00000564992.2 linkuse as main transcript	c.342G>C	p.Thr114=	synonymous_variant	3/4	2	NM_001276309.3	ENSP00000457720	P2

Frequencies

GnomAD3 genomes

AF:

0.000585

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000536

AC:

118

AN:

220318

Hom.:

AF XY:

0.000498

AC XY:

AN XY:

120592

show subpopulations

Gnomad AFR exome

AF:

0.000354

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000129

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000115

Gnomad FIN exome

AF:

0.000153

Gnomad NFE exome

AF:

0.00105

Gnomad OTH exome

AF:

0.000191

GnomAD4 exome

AF:

0.000767

AC:

1097

AN:

1431052

Hom.:

Cov.:

AF XY:

0.000742

AC XY:

527

AN XY:

709768

show subpopulations

Gnomad4 AFR exome

AF:

0.000217

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000415

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000732

Gnomad4 FIN exome

AF:

0.000154

Gnomad4 NFE exome

AF:

0.000948

Gnomad4 OTH exome

AF:

0.000579

GnomAD4 genome

AF:

0.000584

AC:

AN:

152364

Hom.:

Cov.:

AF XY:

0.000564

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000395

Hom.:

Bravo

AF:

0.000476

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000545

AC:

ESP6500EA

AF:

0.000631

AC:

ExAC

AF:

0.000559

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2022

The c.332G>C (p.R111P) alteration is located in exon 3 (coding exon 2) of the NOL3 gene. This alteration results from a G to C substitution at nucleotide position 332, causing the arginine (R) at amino acid position 111 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.74

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.43

M_CAP

Benign

0.058

MetaRNN

Benign

0.029

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.23

Sift

Uncertain

0.0060

Sift4G

Benign

0.17

Vest4

0.43

MVP

0.50

MPC

1.5

GERP RS

-0.66

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over