Variant 7-156950143-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138400.2(NOM1):c.406C>G(p.Arg136Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000951 in 1,577,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000077 ( 0 hom. )

Consequence

NOM1
NM_138400.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.62

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:

NOM1 (HGNC:):

NOM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10257399).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOM1	NM_138400.2 linkuse as main transcript	c.406C>G	p.Arg136Gly	missense_variant	1/11	ENST00000275820.4	NP_612409.1	Q5C9Z4
NOM1	NM_001353366.2 linkuse as main transcript	c.406C>G	p.Arg136Gly	missense_variant	1/11		NP_001340295.1
NOM1	XR_927511.4 linkuse as main transcript	n.432C>G		non_coding_transcript_exon_variant	1/8
NOM1	XR_927513.4 linkuse as main transcript	n.432C>G		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOM1	ENST00000275820.4 linkuse as main transcript	c.406C>G	p.Arg136Gly	missense_variant	1/11	1	NM_138400.2	ENSP00000275820.3		Q5C9Z4

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000271

AC:

AN:

184774

Hom.:

AF XY:

0.0000292

AC XY:

AN XY:

102864

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000150

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000377

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000772

AC:

AN:

1425678

Hom.:

Cov.:

AF XY:

0.00000990

AC XY:

AN XY:

707320

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000266

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000223

Gnomad4 NFE exome

AF:

0.00000729

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000914

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000347

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 31, 2023

The c.406C>G (p.R136G) alteration is located in exon 1 (coding exon 1) of the NOM1 gene. This alteration results from a C to G substitution at nucleotide position 406, causing the arginine (R) at amino acid position 136 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.0051

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.42

M_CAP

Benign

0.014

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.76

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.1

REVEL

Benign

0.080

Sift

Benign

0.20

Sift4G

Benign

0.22

Polyphen

0.80

Vest4

0.19

MutPred

0.26

Loss of solvent accessibility (P = 0.0044);

MVP

0.41

MPC

1.4

ClinPred

0.76

GERP RS

3.7

Varity_R

0.18

gMVP

0.15

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over