19-49908372-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_016553.5(NUP62):c.1436A>G(p.Asn479Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000235 in 1,614,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000020 ( 0 hom. )
Consequence
NUP62
NM_016553.5 missense
NM_016553.5 missense
Scores
3
9
6
Clinical Significance
Conservation
PhyloP100: 6.07
Genes affected
NUP62 (HGNC:8066): (nucleoporin 62) The nuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm. Nucleoporins are the main components of the nuclear pore complex in eukaryotic cells. The protein encoded by this gene is a member of the FG-repeat containing nucleoporins and is localized to the nuclear pore central plug. This protein associates with the importin alpha/beta complex which is involved in the import of proteins containing nuclear localization signals. Multiple transcript variants of this gene encode a single protein isoform. [provided by RefSeq, Jul 2008]
IL4I1 (HGNC:19094): (interleukin 4 induced 1) This gene encodes a secreted L-amino acid oxidase protein which primarily catabolizes L-phenylalanine and, to a lesser extent, L-arginine. The expression of this gene is induced by the cytokine interleukin 4 in B cells. This gene is also expressed in macrophages and dendritic cells. This protein may play a role immune system escape as it is expressed in tumor-associated macrophages and suppresses T-cell responses. This protein also contains domains thought to be involved in the binding of flavin adenine dinucleotide (FAD) cofactor. Multiple transcript variants encoding different isoforms have been found for this gene. Some transcripts of this gene share a promoter and exons of the 5' UTR with the overlapping NUP62 gene. [provided by RefSeq, Jul 2020]
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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, 0.754
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NUP62 | NM_016553.5 | c.1436A>G | p.Asn479Ser | missense_variant | 3/3 | ENST00000352066.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NUP62 | ENST00000352066.8 | c.1436A>G | p.Asn479Ser | missense_variant | 3/3 | 1 | NM_016553.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152212Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000319 AC: 8AN: 251124Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135762
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GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461866Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13AN XY: 727234
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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 | Invitae | Apr 11, 2023 | This variant is present in population databases (rs139913264, gnomAD 0.01%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 479 of the NUP62 protein (p.Asn479Ser). This variant has not been reported in the literature in individuals affected with NUP62-related conditions. 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1358508). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
D;D;D;.;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;.;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;.;.;.
REVEL
Uncertain
Sift
Pathogenic
D;D;.;.;.
Sift4G
Benign
T;T;T;T;T
Polyphen
B;B;B;.;B
Vest4
MVP
MPC
0.37
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at