Variant rs4280164 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_174913.3(NOP9):c.923G>A(p.Ser308Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,613,460 control chromosomes in the GnomAD database, including 33,859 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.19 ( 3021 hom., cov: 33)

Exomes 𝑓: 0.20 ( 30838 hom. )

Consequence

NOP9
NM_174913.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.17

Variant links:

Genes affected

NOP9 (HGNC:19826): (NOP9 nucleolar protein) Enables RNA binding activity. Predicted to be involved in ribosome biogenesis. Predicted to be part of 90S preribosome and preribosome, small subunit precursor. Predicted to be active in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

NOP9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020207465).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOP9	NM_174913.3 linkuse as main transcript	c.923G>A	p.Ser308Asn	missense_variant	4/10	ENST00000267425.8	NP_777573.1	Q86U38-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NOP9	ENST00000267425.8 linkuse as main transcript	c.923G>A	p.Ser308Asn	missense_variant	4/10	1	NM_174913.3	ENSP00000267425.3	Q86U38-1
NOP9	ENST00000396802.7 linkuse as main transcript	c.923G>A	p.Ser308Asn	missense_variant	4/10	5		ENSP00000380020.3	Q86U38-2
NOP9	ENST00000650565.1 linkuse as main transcript	n.407G>A		non_coding_transcript_exon_variant	3/11			ENSP00000497287.1	A0A3B3ISH6

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28521

AN:

152042

Hom.:

3020

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.287

Gnomad ASJ

AF:

0.188

Gnomad EAS

AF:

0.00192

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.205

Gnomad OTH

AF:

0.189

GnomAD3 exomes

AF:

0.191

AC:

47856

AN:

251178

Hom.:

5831

AF XY:

0.181

AC XY:

24582

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.385

Gnomad ASJ exome

AF:

0.194

Gnomad EAS exome

AF:

0.00158

Gnomad SAS exome

AF:

0.109

Gnomad FIN exome

AF:

0.137

Gnomad NFE exome

AF:

0.196

Gnomad OTH exome

AF:

0.198

GnomAD4 exome

AF:

0.197

AC:

287201

AN:

1461300

Hom.:

30838

Cov.:

AF XY:

0.193

AC XY:

140155

AN XY:

726938

show subpopulations

Gnomad4 AFR exome

AF:

0.167

Gnomad4 AMR exome

AF:

0.372

Gnomad4 ASJ exome

AF:

0.196

Gnomad4 EAS exome

AF:

0.000781

Gnomad4 SAS exome

AF:

0.113

Gnomad4 FIN exome

AF:

0.142

Gnomad4 NFE exome

AF:

0.208

Gnomad4 OTH exome

AF:

0.184

GnomAD4 genome

AF:

0.188

AC:

28534

AN:

152160

Hom.:

3021

Cov.:

AF XY:

0.182

AC XY:

13560

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.171

Gnomad4 AMR

AF:

0.287

Gnomad4 ASJ

AF:

0.188

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.106

Gnomad4 FIN

AF:

0.132

Gnomad4 NFE

AF:

0.205

Gnomad4 OTH

AF:

0.187

Alfa

AF:

0.196

Hom.:

8059

Bravo

AF:

0.200

TwinsUK

AF:

0.217

AC:

804

ALSPAC

AF:

0.217

AC:

836

ESP6500AA

AF:

0.167

AC:

736

ESP6500EA

AF:

0.207

AC:

1783

ExAC

AF:

0.183

AC:

22168

Asia WGS

AF:

0.0630

AC:

218

AN:

3478

EpiCase

AF:

0.192

EpiControl

AF:

0.190

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.029

T;.

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.91

MetaRNN

Benign

0.0020

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.32

N;N

REVEL

Benign

0.081

Sift

Benign

0.23

T;T

Sift4G

Uncertain

0.018

D;D

Polyphen

0.94

P;.

Vest4

0.14

MPC

0.44

ClinPred

0.030

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.071

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over