Variant rs12919 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict 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 0.53 ( 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

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 made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NOM1	NM_138400.2 linkuse as main transcript	c.2434G>A	p.Val812Met	missense_variant	11/11	ENST00000275820.4	NP_612409.1
NOM1	NM_001353366.2 linkuse as main transcript	c.2437G>A	p.Val813Met	missense_variant	11/11		NP_001340295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOM1	ENST00000275820.4 linkuse as main transcript	c.2434G>A	p.Val812Met	missense_variant	11/11	1	NM_138400.2	ENSP00000275820	P1
NOM1	ENST00000486131.1 linkuse as main transcript	n.468G>A		non_coding_transcript_exon_variant	2/2	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

GnomAD3 exomes

AF:

0.516

AC:

129185

AN:

250510

Hom.:

34327

AF XY:

0.515

AC XY:

69742

AN XY:

135434

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 SAS exome

AF:

0.467

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

Gnomad4 AFR exome

AF:

0.534

Gnomad4 AMR exome

AF:

0.540

Gnomad4 ASJ exome

AF:

0.623

Gnomad4 EAS exome

AF:

0.281

Gnomad4 SAS exome

AF:

0.467

Gnomad4 FIN exome

AF:

0.458

Gnomad4 NFE exome

AF:

0.560

Gnomad4 OTH exome

AF:

0.547

GnomAD4 genome

AF:

0.533

AC:

80997

AN:

152050

Hom.:

21908

Cov.:

AF XY:

0.526

AC XY:

39054

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.532

Gnomad4 AMR

AF:

0.564

Gnomad4 ASJ

AF:

0.631

Gnomad4 EAS

AF:

0.287

Gnomad4 SAS

AF:

0.451

Gnomad4 FIN

AF:

0.449

Gnomad4 NFE

AF:

0.557

Gnomad4 OTH

AF:

0.583

Alfa

AF:

0.549

Hom.:

53975

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

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

MutationTaster

Benign

1.0

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over