dbSNP rs12919: NOM1:p.Val812Met (chr7-156969554-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_138400.2(NOM1):c.2434G>A(p.Val812Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 1,612,708 control chromosomes in the GnomAD database, including 239,928 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.53 ( 21908 hom., cov: 32)

Exomes 𝑓: 0.54 ( 218020 hom. )

Consequence

NOM1
NM_138400.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.186

Publications

43 publications found

Variant links:

Genes affected

NOM1 (HGNC:13244): (nucleolar protein with MIF4G domain 1) Proteins that contain MIF4G (middle of eIF4G (MIM 600495)) and/or MA3 domains, such as NOM1, function in protein translation. These domains include binding sites for members of the EIF4A family of ATP-dependent DEAD box RNA helicases (see EIF4A1; MIM 602641) (Simmons et al., 2005 [PubMed 15715967]).[supplied by OMIM, Mar 2008]

NOM1 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=9.544928E-6).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOM1	NM_138400.2 link	c.2434G>A	p.Val812Met	missense_variant	Exon 11 of 11	ENST00000275820.4	NP_612409.1	Q5C9Z4
NOM1	NM_001353366.2 link	c.2437G>A	p.Val813Met	missense_variant	Exon 11 of 11		NP_001340295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOM1	ENST00000275820.4 link	c.2434G>A	p.Val812Met	missense_variant	Exon 11 of 11	1	NM_138400.2	ENSP00000275820.3		Q5C9Z4
NOM1	ENST00000486131.1 link	n.468G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.533

AC:

80951

AN:

151932

Hom.:

21900

Cov.:

show subpopulations

Gnomad AFR

AF:

0.532

Gnomad AMI

AF:

0.484

Gnomad AMR

AF:

0.565

Gnomad ASJ

AF:

0.631

Gnomad EAS

AF:

0.288

Gnomad SAS

AF:

0.452

Gnomad FIN

AF:

0.449

Gnomad MID

AF:

0.642

Gnomad NFE

AF:

0.557

Gnomad OTH

AF:

0.581

GnomAD2 exomes

AF:

0.516

AC:

129185

AN:

250510

AF XY:

0.515

show subpopulations

Gnomad AFR exome

AF:

0.534

Gnomad AMR exome

AF:

0.538

Gnomad ASJ exome

AF:

0.623

Gnomad EAS exome

AF:

0.281

Gnomad FIN exome

AF:

0.454

Gnomad NFE exome

AF:

0.558

Gnomad OTH exome

AF:

0.552

GnomAD4 exome

AF:

0.543

AC:

793137

AN:

1460658

Hom.:

218020

Cov.:

AF XY:

0.541

AC XY:

393192

AN XY:

726618

show subpopulations

African (AFR)

AF:

0.534

AC:

17858

AN:

33458

American (AMR)

AF:

0.540

AC:

24087

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.623

AC:

16277

AN:

26114

East Asian (EAS)

AF:

0.281

AC:

11159

AN:

39680

South Asian (SAS)

AF:

0.467

AC:

40194

AN:

86158

European-Finnish (FIN)

AF:

0.458

AC:

24419

AN:

53286

Middle Eastern (MID)

AF:

0.631

AC:

3630

AN:

5754

European-Non Finnish (NFE)

AF:

0.560

AC:

622502

AN:

1111240

Other (OTH)

AF:

0.547

AC:

33011

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

17837

35674

53510

71347

89184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.533

AC:

80997

AN:

152050

Hom.:

21908

Cov.:

AF XY:

0.526

AC XY:

39054

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.532

AC:

22053

AN:

41454

American (AMR)

AF:

0.564

AC:

8614

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.631

AC:

2192

AN:

3472

East Asian (EAS)

AF:

0.287

AC:

1483

AN:

5162

South Asian (SAS)

AF:

0.451

AC:

2173

AN:

4814

European-Finnish (FIN)

AF:

0.449

AC:

4741

AN:

10568

Middle Eastern (MID)

AF:

0.633

AC:

186

AN:

294

European-Non Finnish (NFE)

AF:

0.557

AC:

37880

AN:

67982

Other (OTH)

AF:

0.583

AC:

1234

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1927

3853

5780

7706

9633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.548

Hom.:

104096

Bravo

AF:

0.544

TwinsUK

AF:

0.559

AC:

2071

ALSPAC

AF:

0.560

AC:

2158

ESP6500AA

AF:

0.553

AC:

2437

ESP6500EA

AF:

0.571

AC:

4907

ExAC

AF:

0.515

AC:

62550

Asia WGS

AF:

0.433

AC:

1509

AN:

3478

EpiCase

AF:

0.561

EpiControl

AF:

0.573

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.016

(source)

DANN

Benign

0.044

DEOGEN2

Benign

0.0029

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.088

MetaRNN

Benign

0.0000095

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

PhyloP100

-0.19

PrimateAI

Benign

0.33

PROVEAN

Benign

1.7

REVEL

Benign

0.20

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0020

Vest4

0.026

MPC

0.071

ClinPred

0.00030

GERP RS

-3.1

Varity_R

0.020

gMVP

0.13

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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rs12919

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