1-229441926-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_018230.3(NUP133):āc.3449A>Gā(p.Tyr1150Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,074 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 7.0e-7 ( 0 hom. )
Consequence
NUP133
NM_018230.3 missense
NM_018230.3 missense
Scores
9
10
Clinical Significance
Conservation
PhyloP100: 3.48
Genes affected
NUP133 (HGNC:18016): (nucleoporin 133) The nuclear envelope creates distinct nuclear and cytoplasmic compartments in eukaryotic cells. It consists of two concentric membranes perforated by nuclear pores, large protein complexes that form aqueous channels to regulate the flow of macromolecules between the nucleus and the cytoplasm. These complexes are composed of at least 100 different polypeptide subunits, many of which belong to the nucleoporin family. The nucleoporin protein encoded by this gene displays evolutionarily conserved interactions with other nucleoporins. This protein, which localizes to both sides of the nuclear pore complex at interphase, remains associated with the complex during mitosis and is targeted at early stages to the reforming nuclear envelope. This protein also localizes to kinetochores of mitotic cells. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NUP133 | NM_018230.3 | c.3449A>G | p.Tyr1150Cys | missense_variant | 26/26 | ENST00000261396.6 | NP_060700.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NUP133 | ENST00000261396.6 | c.3449A>G | p.Tyr1150Cys | missense_variant | 26/26 | 1 | NM_018230.3 | ENSP00000261396 | P1 | |
NUP133 | ENST00000490352.1 | n.496A>G | non_coding_transcript_exon_variant | 4/4 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 7.00e-7 AC: 1AN: 1428074Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 709786
GnomAD4 exome
AF:
AC:
1
AN:
1428074
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Cov.:
29
AF XY:
AC XY:
0
AN XY:
709786
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Alfa
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 21, 2022 | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1150 of the NUP133 protein (p.Tyr1150Cys). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with NUP133-related conditions. This variant is not present in population databases (gnomAD no frequency). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Gain of sheet (P = 0.0166);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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