dbSNP rs4280164: NOP9:p.Ser308Asn (chr14-24302079-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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.

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

Publications

54 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NOP9	NM_174913.3 link	c.923G>A	p.Ser308Asn	missense_variant	Exon 4 of 10	ENST00000267425.8	NP_777573.1	Q86U38-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NOP9	ENST00000267425.8 link	c.923G>A	p.Ser308Asn	missense_variant	Exon 4 of 10	1	NM_174913.3	ENSP00000267425.3	Q86U38-1
NOP9	ENST00000396802.7 link	c.923G>A	p.Ser308Asn	missense_variant	Exon 4 of 10	5		ENSP00000380020.3	Q86U38-2
NOP9	ENST00000650565.1 link	n.407G>A		non_coding_transcript_exon_variant	Exon 3 of 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

GnomAD2 exomes

AF:

0.191

AC:

47856

AN:

251178

AF XY:

0.181

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 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

African (AFR)

AF:

0.167

AC:

5600

AN:

33460

American (AMR)

AF:

0.372

AC:

16635

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

5126

AN:

26112

East Asian (EAS)

AF:

0.000781

AC:

AN:

39700

South Asian (SAS)

AF:

0.113

AC:

9747

AN:

86194

European-Finnish (FIN)

AF:

0.142

AC:

7579

AN:

53410

Middle Eastern (MID)

AF:

0.115

AC:

663

AN:

5760

European-Non Finnish (NFE)

AF:

0.208

AC:

230707

AN:

1111608

Other (OTH)

AF:

0.184

AC:

11113

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

11748

23497

35245

46994

58742

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8026

16052

24078

32104

40130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.188

AC:

28534

AN:

152160

Hom.:

3021

Cov.:

AF XY:

0.182

AC XY:

13560

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.171

AC:

7078

AN:

41488

American (AMR)

AF:

0.287

AC:

4394

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.188

AC:

654

AN:

3470

East Asian (EAS)

AF:

0.00193

AC:

AN:

5194

South Asian (SAS)

AF:

0.106

AC:

510

AN:

4822

European-Finnish (FIN)

AF:

0.132

AC:

1397

AN:

10574

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.205

AC:

13955

AN:

68000

Other (OTH)

AF:

0.187

AC:

396

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1180

2360

3540

4720

5900

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

294

588

882

1176

1470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.197

Hom.:

15729

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

(source)

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

PhyloP100

3.2

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

PromoterAI

0.0032

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.071

gMVP

0.19

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over