chr2-183159603-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_138285.5(NUP35):c.854C>T(p.Thr285Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000403 in 1,613,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000042 ( 0 hom. )
Consequence
NUP35
NM_138285.5 missense
NM_138285.5 missense
Scores
9
8
Clinical Significance
Conservation
PhyloP100: 4.70
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 Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2786508).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NUP35 | NM_138285.5 | c.854C>T | p.Thr285Ile | missense_variant | 8/9 | ENST00000295119.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NUP35 | ENST00000295119.9 | c.854C>T | p.Thr285Ile | missense_variant | 8/9 | 1 | NM_138285.5 | P1 | |
NUP35 | ENST00000409798.5 | c.803C>T | p.Thr268Ile | missense_variant | 9/10 | 2 | |||
NUP35 | ENST00000479162.5 | n.751C>T | non_coding_transcript_exon_variant | 7/7 | 2 | ||||
NUP35 | ENST00000374930.7 | c.*253C>T | 3_prime_UTR_variant, NMD_transcript_variant | 7/8 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152096Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251090Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135724
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GnomAD4 exome AF: 0.0000417 AC: 61AN: 1461132Hom.: 0 Cov.: 30 AF XY: 0.0000385 AC XY: 28AN XY: 726894
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152096Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74300
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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 | Nov 29, 2021 | The c.854C>T (p.T285I) alteration is located in exon 8 (coding exon 8) of the NUP35 gene. This alteration results from a C to T substitution at nucleotide position 854, causing the threonine (T) at amino acid position 285 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
0.35
.;B
Vest4
MVP
MPC
0.24
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