16-67174348-G-A

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

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.75
Variant links:
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]

Genome browser will be placed here

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
NOL3NM_001276309.3 linkuse as main transcriptc.179G>A p.Arg60His missense_variant 2/4 ENST00000564992.2 NP_001263238.1
NOL3XM_047434851.1 linkuse as main transcriptc.365G>A p.Arg122His missense_variant 3/5 XP_047290807.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NOL3ENST00000564992.2 linkuse as main transcriptc.179G>A p.Arg60His missense_variant 2/42 NM_001276309.3 ENSP00000457720 P2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000487
AC:
7
AN:
1435968
Hom.:
0
Cov.:
32
AF XY:
0.00000561
AC XY:
4
AN XY:
712756
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:
0.0000358
Gnomad4 FIN exome
AF:
0.0000207
Gnomad4 NFE exome
AF:
0.00000182
Gnomad4 OTH exome
AF:
0.0000168
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

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 09, 2024The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Benign
-0.058
T
BayesDel_noAF
Benign
-0.32
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.047
T;T;T;.;.;.
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Benign
0.71
D
LIST_S2
Uncertain
0.86
D;D;D;D;D;D
M_CAP
Benign
0.061
D
MetaRNN
Benign
0.41
T;T;T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.4
.;.;L;.;.;L
MutationTaster
Benign
0.78
D;D;D;D
PrimateAI
Uncertain
0.76
T
PROVEAN
Uncertain
-3.3
D;D;N;N;D;D
REVEL
Benign
0.23
Sift
Uncertain
0.0030
D;D;D;.;.;D
Sift4G
Benign
0.22
T;D;T;T;T;D
Polyphen
1.0
.;.;D;.;.;.
Vest4
0.39, 0.45, 0.36
MutPred
0.56
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
0.45
MPC
1.4
ClinPred
0.98
D
GERP RS
4.0
Varity_R
0.55

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs996335051; hg19: chr16-67208251; API