19-47750277-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015710.5(NOP53):​c.389C>T​(p.Ala130Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000534 in 1,592,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A130S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

NOP53
NM_015710.5 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.395
Variant links:
Genes affected
NOP53 (HGNC:4333): (NOP53 ribosome biogenesis factor) Enables 5S rRNA binding activity; identical protein binding activity; and p53 binding activity. Involved in several processes, including negative regulation of transcription, DNA-templated; regulation of cellular protein metabolic process; and regulation of intracellular signal transduction. Located in cytosol; fibrillar center; and nucleoplasm. Colocalizes with rDNA heterochromatin. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.013990045).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NOP53NM_015710.5 linkc.389C>T p.Ala130Val missense_variant Exon 3 of 13 ENST00000246802.10 NP_056525.2 Q9NZM5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NOP53ENST00000246802.10 linkc.389C>T p.Ala130Val missense_variant Exon 3 of 13 1 NM_015710.5 ENSP00000246802.4 Q9NZM5

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152196
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000271
AC:
68
AN:
251300
Hom.:
0
AF XY:
0.000213
AC XY:
29
AN XY:
135874
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00194
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:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000555
AC:
80
AN:
1440620
Hom.:
0
Cov.:
25
AF XY:
0.0000460
AC XY:
33
AN XY:
717976
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00175
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:
0.00
Gnomad4 OTH exome
AF:
0.0000335
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152196
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000749
Hom.:
0
Bravo
AF:
0.0000869
ExAC
AF:
0.000165
AC:
20

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 14, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.389C>T (p.A130V) alteration is located in exon 3 (coding exon 3) of the GLTSCR2 gene. This alteration results from a C to T substitution at nucleotide position 389, causing the alanine (A) at amino acid position 130 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided Uncertain:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.071
BayesDel_addAF
Benign
-0.63
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
12
DANN
Benign
0.88
DEOGEN2
Benign
0.027
T;.
Eigen
Benign
-0.76
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.16
N
LIST_S2
Benign
0.80
T;T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.014
T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.65
N;.
REVEL
Benign
0.059
Sift
Benign
0.22
T;.
Sift4G
Benign
0.20
T;T
Polyphen
0.0040
B;.
Vest4
0.15
MutPred
0.51
Loss of ubiquitination at K127 (P = 0.0431);.;
MVP
0.26
MPC
0.20
ClinPred
0.010
T
GERP RS
0.013
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3
Varity_R
0.056
gMVP
0.11

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: rs779428264; hg19: chr19-48253534; COSMIC: COSV99884110; COSMIC: COSV99884110; API