Genetic Variant NOL11:p.Pro53Arg (chr17-67719690-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015462.5(NOL11):c.158C>G(p.Pro53Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000501 in 1,596,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

NOL11
NM_015462.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.82

Variant links:

Genes affected

NOL11 (HGNC:24557): (nucleolar protein 11) Enables RNA binding activity. Involved in maturation of SSU-rRNA and positive regulation of transcription of nucleolar large rRNA by RNA polymerase I. Located in nucleolus. Part of t-UTP complex. [provided by Alliance of Genome Resources, Apr 2022]

NOL11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.745

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOL11	NM_015462.5 link	c.158C>G	p.Pro53Arg	missense_variant	Exon 2 of 18	ENST00000253247.9	NP_056277.2	Q9H8H0-1
NOL11	NM_001303272.2 link	c.-331C>G		5_prime_UTR_variant	Exon 2 of 17		NP_001290201.1	Q9H8H0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOL11	ENST00000253247.9 link	c.158C>G	p.Pro53Arg	missense_variant	Exon 2 of 18	1	NM_015462.5	ENSP00000253247.4		Q9H8H0-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151914

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000807

AC:

AN:

247712

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133752

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.00

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:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000415

AC:

AN:

1444186

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

719140

show subpopulations

Gnomad4 AFR exome

AF:

0.0000606

Gnomad4 AMR exome

AF:

0.00

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:

0.00000364

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151914

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74170

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 19, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.158C>G (p.P53R) alteration is located in exon 2 (coding exon 2) of the NOL11 gene. This alteration results from a C to G substitution at nucleotide position 158, causing the proline (P) at amino acid position 53 to be replaced by an arginine (R). 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

Pathogenic

0.61

BayesDel_addAF

Uncertain

0.016

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

DANN

Benign

0.95

DEOGEN2

Benign

0.28

T;.

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.022

MetaRNN

Pathogenic

0.75

D;D

MetaSVM

Benign

-0.39

MutationAssessor

Uncertain

2.8

M;.

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.4

D;.

REVEL

Uncertain

0.41

Sift

Uncertain

0.0090

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.85

MVP

0.84

MPC

0.58

ClinPred

0.95

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.53

gMVP

0.65

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