Genetic Variant NOL10:p.Val473Ile (chr2-10600858-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024894.4(NOL10):c.1417G>A(p.Val473Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NOL10
NM_024894.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.54

Publications

0 publications found

Variant links:

Genes affected

NOL10 (HGNC:25862): (nucleolar protein 10) Enables RNA binding activity. Predicted to be involved in maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

NOL10 links:

ENSG00000234818 (HGNC:):

ENSG00000234818 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04046142).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024894.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOL10	NM_024894.4	MANE Select	c.1417G>A	p.Val473Ile	missense	Exon 17 of 21	NP_079170.2	Q9BSC4-1
NOL10	NM_001261392.2		c.1339G>A	p.Val447Ile	missense	Exon 16 of 20	NP_001248321.1	Q9BSC4-4
NOL10	NM_001261394.2		c.1267G>A	p.Val423Ile	missense	Exon 16 of 20	NP_001248323.1	Q9BSC4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOL10	ENST00000381685.10	TSL:1 MANE Select	c.1417G>A	p.Val473Ile	missense	Exon 17 of 21	ENSP00000371101.5	Q9BSC4-1
NOL10	ENST00000695468.1		c.1468G>A	p.Val490Ile	missense	Exon 18 of 22	ENSP00000511946.1	A0A8Q3SHX7
NOL10	ENST00000928635.1		c.1438G>A	p.Val480Ile	missense	Exon 17 of 21	ENSP00000598694.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1393310

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

687634

African (AFR)

AF:

0.00

AC:

AN:

31650

American (AMR)

AF:

0.00

AC:

AN:

35704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25122

East Asian (EAS)

AF:

0.00

AC:

AN:

36260

South Asian (SAS)

AF:

0.00

AC:

AN:

78224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1073476

Other (OTH)

AF:

0.00

AC:

AN:

57800

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0031

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.78

M_CAP

Benign

0.0066

MetaRNN

Benign

0.040

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

1.5

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.50

REVEL

Benign

0.031

Sift

Benign

0.20

Sift4G

Benign

0.18

Polyphen

0.0060

Vest4

0.098

MutPred

0.17

Gain of methylation at K470 (P = 0.0634)

MVP

0.13

MPC

0.090

ClinPred

0.083

GERP RS

0.30

Varity_R

0.030

gMVP

0.047

Mutation Taster

=96/4

polymorphism

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over