Variant 16-67174656-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000564992.2(NOL3):c.331G>A(p.Gly111Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000293 in 1,574,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. G111G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

NOL3
ENST00000564992.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.05

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=0.013244212).

BP6

Variant 16-67174656-G-A is Benign according to our data. Variant chr16-67174656-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 717334.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 63 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOL3	NM_001276309.3 linkuse as main transcript	c.331G>A	p.Gly111Ser	missense_variant	3/4	ENST00000564992.2	NP_001263238.1
NOL3	XM_047434851.1 linkuse as main transcript	c.517G>A	p.Gly173Ser	missense_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.331G>A	p.Gly111Ser	missense_variant	3/4	2	NM_001276309.3	ENSP00000457720	P2

Frequencies

GnomAD3 genomes

AF:

0.000414

AC:

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00163

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000348

AC:

AN:

212468

Hom.:

AF XY:

0.000328

AC XY:

AN XY:

115864

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000688

Gnomad ASJ exome

AF:

0.00261

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000349

Gnomad OTH exome

AF:

0.000397

GnomAD4 exome

AF:

0.000280

AC:

398

AN:

1422400

Hom.:

Cov.:

AF XY:

0.000301

AC XY:

212

AN XY:

704702

show subpopulations

Gnomad4 AFR exome

AF:

0.0000312

Gnomad4 AMR exome

AF:

0.000827

Gnomad4 ASJ exome

AF:

0.00214

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.0000195

Gnomad4 NFE exome

AF:

0.000269

Gnomad4 OTH exome

AF:

0.000325

GnomAD4 genome

AF:

0.000413

AC:

AN:

152382

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000412

Hom.:

Bravo

AF:

0.000412

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000377

AC:

ExAC

AF:

0.000275

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.083

T;T;T;.;.

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.75

T;T;T;T;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.013

T;T;T;T;T

MetaSVM

Benign

-0.37

MutationTaster

Benign

0.88

D;D;D;D

PROVEAN

Benign

-2.0

N;N;N;N;N

REVEL

Benign

0.089

Sift

Pathogenic

0.0

D;D;D;.;.

Sift4G

Benign

0.31

T;D;T;T;T

Vest4

0.37, 0.38

MVP

0.44

ClinPred

0.13

GERP RS

3.9

Varity_R

0.29

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