12-68689593-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_020401.4(NUP107):c.161G>A(p.Arg54Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000776 in 1,611,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.00051 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00080 ( 0 hom. )
Consequence
NUP107
NM_020401.4 missense
NM_020401.4 missense
Scores
1
2
13
Clinical Significance
Conservation
PhyloP100: 2.92
Genes affected
NUP107 (HGNC:29914): (nucleoporin 107) This gene encodes a member of the nucleoporin family. The protein is localized to the nuclear rim and is an essential component of the nuclear pore complex (NPC). All molecules entering or leaving the nucleus either diffuse through or are actively transported by the NPC. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [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 | UniProt |
|---|---|---|---|---|---|---|---|
| NUP107 | NM_020401.4 | c.161G>A | p.Arg54Gln | missense_variant | 3/28 | ENST00000229179.9 | |
| NUP107 | NM_001330192.2 | c.46G>A | p.Glu16Lys | missense_variant | 3/28 | ||
| NUP107 | XM_005269037.5 | c.161G>A | p.Arg54Gln | missense_variant | 3/27 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NUP107 | ENST00000229179.9 | c.161G>A | p.Arg54Gln | missense_variant | 3/28 | 1 | NM_020401.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000513 AC: 78AN: 151990Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000493 AC: 123AN: 249514Hom.: 0 AF XY: 0.000430 AC XY: 58AN XY: 134954
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GnomAD4 exome AF: 0.000803 AC: 1172AN: 1459352Hom.: 0 Cov.: 29 AF XY: 0.000773 AC XY: 561AN XY: 726038
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GnomAD4 genome ? AF: 0.000513 AC: 78AN: 152108Hom.: 0 Cov.: 33 AF XY: 0.000444 AC XY: 33AN XY: 74342
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 17, 2021 | The c.161G>A (p.R54Q) alteration is located in exon 3 (coding exon 3) of the NUP107 gene. This alteration results from a G to A substitution at nucleotide position 161, causing the arginine (R) at amino acid position 54 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 16, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 54 of the NUP107 protein (p.Arg54Gln). This variant is present in population databases (rs139991199, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with NUP107-related conditions. ClinVar contains an entry for this variant (Variation ID: 2198280). 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 tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;N
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Pathogenic
D
Vest4
MVP
ClinPred
T
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 26
Find out detailed SpliceAI scores and Pangolin per-transcript scores at