16-67174348-G-A
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The ENST00000568146.1(NOL3):c.179G>A(p.Arg60His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000487 in 1,435,968 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: not found (cov: 33)
Exomes 𝑓: 0.0000049 ( 0 hom. )
Consequence
NOL3
ENST00000568146.1 missense
ENST00000568146.1 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 1.75
Genes affected
NOL3 (HGNC:7869): (nucleolar protein 3) This gene encodes an anti-apoptotic protein that has been shown to down-regulate the enzyme activities of caspase 2, caspase 8 and tumor protein p53. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.4109638).
BS2
High AC in GnomAdExome4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NOL3 | NM_001276309.3 | c.179G>A | p.Arg60His | missense_variant | 2/4 | ENST00000564992.2 | NP_001263238.1 | |
NOL3 | XM_047434851.1 | c.365G>A | p.Arg122His | missense_variant | 3/5 | XP_047290807.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NOL3 | ENST00000564992.2 | c.179G>A | p.Arg60His | missense_variant | 2/4 | 2 | NM_001276309.3 | ENSP00000457720 | P2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000487 AC: 7AN: 1435968Hom.: 0 Cov.: 32 AF XY: 0.00000561 AC XY: 4AN XY: 712756
GnomAD4 exome
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AC:
7
AN:
1435968
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Cov.:
32
AF XY:
AC XY:
4
AN XY:
712756
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
Bravo
AF:
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 submitter | clinical testing | Ambry Genetics | Apr 09, 2024 | The c.179G>A (p.R60H) alteration is located in exon 2 (coding exon 1) of the NOL3 gene. This alteration results from a G to A substitution at nucleotide position 179, causing the arginine (R) at amino acid position 60 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T;T;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;L;.;.;L
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;N;N;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;.;.;D
Sift4G
Benign
T;D;T;T;T;D
Polyphen
1.0
.;.;D;.;.;.
Vest4
0.39, 0.45, 0.36
MutPred
Loss of MoRF binding (P = 0.0127);Loss of MoRF binding (P = 0.0127);Loss of MoRF binding (P = 0.0127);Loss of MoRF binding (P = 0.0127);.;Loss of MoRF binding (P = 0.0127);
MVP
MPC
1.4
ClinPred
D
GERP RS
Varity_R
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at