Variant chr16-67174245-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000568146.1(NOL3):c.76G>T(p.Asp26Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000825 in 1,612,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

NOL3
ENST00000568146.1 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.60

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.052060902).

BP6

Variant 16-67174245-G-T is Benign according to our data. Variant chr16-67174245-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3047843.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOL3	NM_001276309.3 linkuse as main transcript	c.76G>T	p.Asp26Tyr	missense_variant	2/4	ENST00000564992.2	NP_001263238.1
NOL3	XM_047434851.1 linkuse as main transcript	c.262G>T	p.Asp88Tyr	missense_variant	3/5		XP_047290807.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOL3	ENST00000564992.2 linkuse as main transcript	c.76G>T	p.Asp26Tyr	missense_variant	2/4	2	NM_001276309.3	ENSP00000457720	P2

Frequencies

GnomAD3 genomes

AF:

0.0000525

AC:

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000479

AC:

116

AN:

242082

Hom.:

AF XY:

0.000278

AC XY:

AN XY:

132860

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00339

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000856

AC:

125

AN:

1460474

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

726540

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000253

ExAC

AF:

0.000416

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NOL3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 23, 2022

This variant is classified as likely 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

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;T;T;.;.;.

Eigen

Benign

0.075

Eigen_PC

Benign

-0.0012

FATHMM_MKL

Benign

0.52

LIST_S2

Uncertain

0.86

D;D;D;D;D;D

M_CAP

Benign

0.062

MetaRNN

Benign

0.052

T;T;T;T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.0

.;.;M;.;.;M

MutationTaster

Benign

0.97

D;D;D;D

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-8.2

D;D;D;D;D;D

REVEL

Uncertain

0.38

Sift

Pathogenic

0.0

D;D;D;.;.;D

Sift4G

Uncertain

0.0040

D;D;D;D;D;D

Polyphen

0.99

.;.;D;.;.;.

Vest4

0.74, 0.75, 0.68

MutPred

0.65

Loss of disorder (P = 0.0107);Loss of disorder (P = 0.0107);Loss of disorder (P = 0.0107);Loss of disorder (P = 0.0107);.;Loss of disorder (P = 0.0107);

MVP

0.74

MPC

1.4

ClinPred

0.33

GERP RS

4.0

Varity_R

0.99

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