Genetic Variant NM_014062.3:c.692G>A (chr16-69748952-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3BA1

The NM_014062.3(NOB1):c.692G>A(p.Arg231Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 1,611,064 control chromosomes in the GnomAD database, including 247,806 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.44 ( 17411 hom., cov: 33)

Exomes 𝑓: 0.55 ( 230395 hom. )

Consequence

NOB1
NM_014062.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.410

Publications

36 publications found

Variant links:

Genes affected

NOB1 (HGNC:29540): (NIN1 (RPN12) binding protein 1 homolog) In yeast, over 200 protein and RNA cofactors are required for ribosome assembly, and these are generally conserved in eukaryotes. These factors orchestrate modification and cleavage of the initial 35S precursor rRNA transcript into the mature 18S, 5.8S, and 25S rRNAs, folding of the rRNA, and binding of ribosomal proteins and 5S RNA. Nob1 is involved in pre-rRNA processing. In a late cytoplasmic processing step, Nob1 cleaves a 20S rRNA intermediate at cleavage site D to produce the mature 18S rRNA (Lamanna and Karbstein, 2009 [PubMed 19706509]).[supplied by OMIM, Nov 2010]

NOB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOB1	NM_014062.3 link	c.692G>A	p.Arg231Gln	missense_variant	Exon 6 of 9	ENST00000268802.10	NP_054781.1	Q9ULX3
NOB1	NR_074074.2 link	n.577G>A		non_coding_transcript_exon_variant	Exon 5 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOB1	ENST00000268802.10 link	c.692G>A	p.Arg231Gln	missense_variant	Exon 6 of 9	1	NM_014062.3	ENSP00000268802.5		Q9ULX3

Frequencies

GnomAD3 genomes

AF:

0.440

AC:

66846

AN:

152078

Hom.:

17421

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.546

Gnomad AMR

AF:

0.463

Gnomad ASJ

AF:

0.559

Gnomad EAS

AF:

0.197

Gnomad SAS

AF:

0.460

Gnomad FIN

AF:

0.584

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.585

Gnomad OTH

AF:

0.459

GnomAD2 exomes

AF:

0.494

AC:

122096

AN:

247368

AF XY:

0.504

show subpopulations

Gnomad AFR exome

AF:

0.165

Gnomad AMR exome

AF:

0.433

Gnomad ASJ exome

AF:

0.548

Gnomad EAS exome

AF:

0.182

Gnomad FIN exome

AF:

0.597

Gnomad NFE exome

AF:

0.587

Gnomad OTH exome

AF:

0.521

GnomAD4 exome

AF:

0.554

AC:

807635

AN:

1458868

Hom.:

230395

Cov.:

AF XY:

0.554

AC XY:

401850

AN XY:

725408

show subpopulations

African (AFR)

AF:

0.159

AC:

5307

AN:

33446

American (AMR)

AF:

0.440

AC:

19484

AN:

44296

Ashkenazi Jewish (ASJ)

AF:

0.544

AC:

14176

AN:

26078

East Asian (EAS)

AF:

0.241

AC:

9559

AN:

39650

South Asian (SAS)

AF:

0.485

AC:

41703

AN:

86066

European-Finnish (FIN)

AF:

0.602

AC:

32087

AN:

53324

Middle Eastern (MID)

AF:

0.468

AC:

2652

AN:

5668

European-Non Finnish (NFE)

AF:

0.587

AC:

651499

AN:

1110066

Other (OTH)

AF:

0.517

AC:

31168

AN:

60274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

19695

39389

59084

78778

98473

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17550

35100

52650

70200

87750

<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:

0.439

AC:

66832

AN:

152196

Hom.:

17411

Cov.:

AF XY:

0.436

AC XY:

32446

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.169

AC:

7015

AN:

41542

American (AMR)

AF:

0.463

AC:

7076

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.559

AC:

1942

AN:

3472

East Asian (EAS)

AF:

0.197

AC:

1018

AN:

5166

South Asian (SAS)

AF:

0.460

AC:

2214

AN:

4818

European-Finnish (FIN)

AF:

0.584

AC:

6198

AN:

10604

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.585

AC:

39781

AN:

67992

Other (OTH)

AF:

0.456

AC:

963

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1743

3486

5228

6971

8714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

604

1208

1812

2416

3020

<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:

0.509

Hom.:

25542

Bravo

AF:

0.416

TwinsUK

AF:

0.591

AC:

2192

ALSPAC

AF:

0.578

AC:

2227

ESP6500AA

AF:

0.180

AC:

792

ESP6500EA

AF:

0.570

AC:

4906

ExAC

AF:

0.492

AC:

59762

Asia WGS

AF:

0.371

AC:

1294

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0062

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.84

MetaRNN

Benign

0.000027

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.1

PhyloP100

-0.41

PrimateAI

Benign

0.23

PROVEAN

Benign

0.12

REVEL

Benign

0.071

Sift

Benign

0.64

Sift4G

Benign

0.56

Polyphen

0.0030

Vest4

0.030

MPC

0.15

ClinPred

0.0011

GERP RS

1.1

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.7

Varity_R

0.055

gMVP

0.18

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.78

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.78

Position offset: -1

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