chr2-183130497-C-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_138285.5(NUP35):c.291C>G(p.Asp97Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,605,542 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00013 ( 1 hom. )
Consequence
NUP35
NM_138285.5 missense
NM_138285.5 missense
Scores
3
14
Clinical Significance
Conservation
PhyloP100: -0.101
Genes affected
NUP35 (HGNC:29797): (nucleoporin 35) This gene encodes a member of the nucleoporin family. The encoded protein contains two membrane binding regions, is localized to the nuclear rim, and is part of the nuclear pore complex. All molecules entering or leaving the nucleus either diffuse through or are actively transported by the nuclear pore complex. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene have been defined on chromosomes 7 and 10. [provided by RefSeq, Dec 2013]
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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=0.01660487).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NUP35 | NM_138285.5 | c.291C>G | p.Asp97Glu | missense_variant | 3/9 | ENST00000295119.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NUP35 | ENST00000295119.9 | c.291C>G | p.Asp97Glu | missense_variant | 3/9 | 1 | NM_138285.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000156 AC: 23AN: 147050Hom.: 0 Cov.: 31
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000307 AC: 77AN: 251202Hom.: 1 AF XY: 0.000243 AC XY: 33AN XY: 135774
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GnomAD4 exome AF: 0.000133 AC: 194AN: 1458394Hom.: 1 Cov.: 33 AF XY: 0.000124 AC XY: 90AN XY: 725544
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GnomAD4 genome ? AF: 0.000156 AC: 23AN: 147148Hom.: 0 Cov.: 31 AF XY: 0.0000981 AC XY: 7AN XY: 71322
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 23, 2023 | The c.291C>G (p.D97E) alteration is located in exon 3 (coding exon 3) of the NUP35 gene. This alteration results from a C to G substitution at nucleotide position 291, causing the aspartic acid (D) at amino acid position 97 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
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
Benign
N
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
0.0
.;.;B
Vest4
0.14, 0.16
MutPred
0.30
.;.;Gain of sheet (P = 0.1208);
MVP
MPC
0.18
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
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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