Variant 2-202302986-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015934.5(NOP58):c.1468A>G(p.Arg490Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,612,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

NOP58
NM_015934.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.40

Variant links:

Genes affected

NOP58 (HGNC:29926): (NOP58 ribonucleoprotein) The protein encoded by this gene is a core component of box C/D small nucleolar ribonucleoproteins. Some box C/D small nucleolar RNAs (snoRNAs), such as U3, U8, and U14, are dependent upon the encoded protein for their synthesis. This protein is SUMOylated, which is necessary for high affinity binding to snoRNAs. [provided by RefSeq, Nov 2015]

NOP58 links:

ENSG00000286223 (HGNC:):

ENSG00000286223 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.068663925).

BS2

High AC in GnomAd4 at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOP58	NM_015934.5 link	c.1468A>G	p.Arg490Gly	missense_variant	Exon 14 of 15	ENST00000264279.10	NP_057018.1	Q9Y2X3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NOP58	ENST00000264279.10 link	c.1468A>G	p.Arg490Gly	missense_variant	Exon 14 of 15	1	NM_015934.5	ENSP00000264279.5	Q9Y2X3
NOP58	ENST00000478508.1 link	n.480A>G		non_coding_transcript_exon_variant	Exon 3 of 4	2
ENSG00000286223	ENST00000652719.1 link	n.277-21T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000202

AC:

AN:

247880

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134288

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1459908

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726318

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000151

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.000219

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1468A>G (p.R490G) alteration is located in exon 14 (coding exon 14) of the NOP58 gene. This alteration results from a A to G substitution at nucleotide position 1468, causing the arginine (R) at amino acid position 490 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

0.17

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.052

Eigen

Benign

-0.14

Eigen_PC

Benign

0.086

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.51

M_CAP

Benign

0.018

MetaRNN

Benign

0.069

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-2.2

REVEL

Benign

0.094

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.031

Polyphen

0.0

Vest4

0.24

MVP

0.26

MPC

0.51

ClinPred

0.18

GERP RS

5.3

Varity_R

0.17

gMVP

0.054

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