chr1-229441943-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_018230.3(NUP133):​c.3432G>C​(p.Leu1144Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

NUP133
NM_018230.3 missense

Scores

1
14
4

Clinical Significance

Uncertain significance no assertion criteria provided U:2

Conservation

PhyloP100: 1.65
Variant links:
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.791

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NUP133NM_018230.3 linkuse as main transcriptc.3432G>C p.Leu1144Phe missense_variant 26/26 ENST00000261396.6 NP_060700.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NUP133ENST00000261396.6 linkuse as main transcriptc.3432G>C p.Leu1144Phe missense_variant 26/261 NM_018230.3 ENSP00000261396 P1
NUP133ENST00000490352.1 linkuse as main transcriptn.479G>C non_coding_transcript_exon_variant 4/42

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

not provided Uncertain:2
Uncertain significance, flagged submissionliterature onlyRichard Lifton Laboratory, Yale University School of Medicine-- -
Uncertain significance, no assertion criteria providedliterature onlyRichard Lifton Laboratory, Yale University School of Medicine-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.36
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.71
D
Eigen
Uncertain
0.25
Eigen_PC
Benign
0.20
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.035
D
MetaRNN
Pathogenic
0.79
D
MetaSVM
Benign
-0.78
T
MutationAssessor
Uncertain
2.6
M
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.76
T
PROVEAN
Uncertain
-3.0
D
REVEL
Uncertain
0.35
Sift
Uncertain
0.0090
D
Sift4G
Uncertain
0.014
D
Polyphen
1.0
D
Vest4
0.73
MutPred
0.44
Loss of helix (P = 0.0304);
MVP
0.48
MPC
0.66
ClinPred
0.97
D
GERP RS
2.7
Varity_R
0.33
gMVP
0.62

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: rs483352747; hg19: chr1-229577690; API