Genetic Variant NOL10:p.Arg530Ser (chr2-10589586-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024894.4(NOL10):c.1588C>A(p.Arg530Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,408,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R530C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

NOL10
NM_024894.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.60

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.069227636).

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.1588C>A	p.Arg530Ser	missense	Exon 18 of 21	NP_079170.2	Q9BSC4-1
NOL10	NM_001261392.2		c.1510C>A	p.Arg504Ser	missense	Exon 17 of 20	NP_001248321.1	Q9BSC4-4
NOL10	NM_001261394.2		c.1438C>A	p.Arg480Ser	missense	Exon 17 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.1588C>A	p.Arg530Ser	missense	Exon 18 of 21	ENSP00000371101.5	Q9BSC4-1
NOL10	ENST00000695468.1		c.1639C>A	p.Arg547Ser	missense	Exon 19 of 22	ENSP00000511946.1	A0A8Q3SHX7
NOL10	ENST00000928635.1		c.1609C>A	p.Arg537Ser	missense	Exon 18 of 21	ENSP00000598694.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.10e-7

AC:

AN:

1408648

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

697942

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

30688

American (AMR)

AF:

0.00

AC:

AN:

31688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23652

East Asian (EAS)

AF:

0.00

AC:

AN:

39058

South Asian (SAS)

AF:

0.00

AC:

AN:

75504

European-Finnish (FIN)

AF:

0.0000193

AC:

AN:

51820

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5496

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1092646

Other (OTH)

AF:

0.00

AC:

AN:

58096

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.00037

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.60

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.37

M_CAP

Benign

0.0080

MetaRNN

Benign

0.069

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

2.6

PrimateAI

Benign

0.21

PROVEAN

Benign

0.34

REVEL

Benign

0.064

Sift

Benign

0.76

Sift4G

Benign

0.80

Polyphen

0.0

Vest4

0.17

MutPred

0.21

Gain of phosphorylation at R530 (P = 8e-04)

MVP

0.29

MPC

0.13

ClinPred

0.12

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.099

gMVP

0.038

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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