17-67718002-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015462.5(NOL11):​c.55C>T​(p.Pro19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NOL11
NM_015462.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.089600205).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NOL11NM_015462.5 linkc.55C>T p.Pro19Ser missense_variant Exon 1 of 18 ENST00000253247.9 NP_056277.2 Q9H8H0-1
NOL11NM_001303272.2 linkc.-434C>T 5_prime_UTR_variant Exon 1 of 17 NP_001290201.1 Q9H8H0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NOL11ENST00000253247.9 linkc.55C>T p.Pro19Ser missense_variant Exon 1 of 18 1 NM_015462.5 ENSP00000253247.4 Q9H8H0-1
NOL11ENST00000581106.5 linkc.55C>T p.Pro19Ser missense_variant Exon 1 of 6 3 ENSP00000463662.1 J3QLQ6
NOL11ENST00000581375.5 linkn.55C>T non_coding_transcript_exon_variant Exon 1 of 17 2 ENSP00000463219.1 Q9H8H0-2
NOL11ENST00000581966.5 linkn.58C>T non_coding_transcript_exon_variant Exon 1 of 5 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251460
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461888
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.55C>T (p.P19S) alteration is located in exon 1 (coding exon 1) of the NOL11 gene. This alteration results from a C to T substitution at nucleotide position 55, causing the proline (P) at amino acid position 19 to be replaced by a serine (S). 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
0.089
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
12
DANN
Benign
0.83
DEOGEN2
Benign
0.0059
T;.
Eigen
Benign
-0.64
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.20
N
LIST_S2
Benign
0.67
T;T
M_CAP
Benign
0.0089
T
MetaRNN
Benign
0.090
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.4
M;.
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.96
N;.
REVEL
Benign
0.065
Sift
Benign
0.17
T;.
Sift4G
Benign
0.73
T;T
Polyphen
0.0
B;.
Vest4
0.097
MutPred
0.38
Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);
MVP
0.42
MPC
0.12
ClinPred
0.12
T
GERP RS
3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.041
gMVP
0.16

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: rs1364926442; hg19: chr17-65714118; API