chr2-10589194-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000381685.10(NOL10):​c.1693C>T​(p.Arg565Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000973 in 1,613,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000098 ( 0 hom. )

Consequence

NOL10
ENST00000381685.10 missense

Scores

5
2
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.27
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.38106126).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NOL10NM_024894.4 linkuse as main transcriptc.1693C>T p.Arg565Cys missense_variant 19/21 ENST00000381685.10 NP_079170.2 Q9BSC4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NOL10ENST00000381685.10 linkuse as main transcriptc.1693C>T p.Arg565Cys missense_variant 19/211 NM_024894.4 ENSP00000371101.5 Q9BSC4-1

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152170
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000956
AC:
24
AN:
251168
Hom.:
0
AF XY:
0.000125
AC XY:
17
AN XY:
135732
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000159
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000978
AC:
143
AN:
1461704
Hom.:
0
Cov.:
31
AF XY:
0.000117
AC XY:
85
AN XY:
727134
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000116
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000919
AC:
14
AN:
152288
Hom.:
0
Cov.:
32
AF XY:
0.0000671
AC XY:
5
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.0000722
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000212
Hom.:
0
Bravo
AF:
0.0000529
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.000124
AC:
15
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000296

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 submitterclinical testingAmbry GeneticsApr 26, 2023The c.1693C>T (p.R565C) alteration is located in exon 19 (coding exon 19) of the NOL10 gene. This alteration results from a C to T substitution at nucleotide position 1693, causing the arginine (R) at amino acid position 565 to be replaced by a cysteine (C). 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
0.24
BayesDel_addAF
Benign
-0.091
T
BayesDel_noAF
Benign
-0.11
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.039
.;.;T
Eigen
Pathogenic
0.77
Eigen_PC
Pathogenic
0.78
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
D;D;D
M_CAP
Benign
0.053
D
MetaRNN
Benign
0.38
T;T;T
MetaSVM
Benign
-0.65
T
MutationAssessor
Benign
2.0
.;.;M
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.50
T
PROVEAN
Uncertain
-2.8
D;D;D
REVEL
Benign
0.24
Sift
Benign
0.039
D;D;D
Sift4G
Benign
0.17
T;T;T
Polyphen
1.0
D;.;D
Vest4
0.59
MVP
0.36
MPC
0.33
ClinPred
0.56
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.36
gMVP
0.14

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.

Other links and lift over

dbSNP: rs546811374; hg19: chr2-10729320; COSMIC: COSV100630317; API