chr5-62504670-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_016338.5(IPO11):c.1594C>T(p.Arg532Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,094 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000069 ( 0 hom. )
Consequence
IPO11
NM_016338.5 missense
NM_016338.5 missense
Scores
11
5
3
Clinical Significance
Conservation
PhyloP100: 7.01
Genes affected
IPO11 (HGNC:20628): (importin 11) Importins, including IPO11, are a members of the karyopherin/importin-beta family of transport receptors (see KPNB1; 602738) that mediate nucleocytoplasmic transport of protein and RNA cargoes (Plafker and Macara, 2000 [PubMed 11032817]).[supplied by OMIM, Sep 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.889
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IPO11 | NM_016338.5 | c.1594C>T | p.Arg532Cys | missense_variant | 17/30 | ENST00000325324.11 | |
IPO11 | NM_001134779.2 | c.1714C>T | p.Arg572Cys | missense_variant | 17/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IPO11 | ENST00000325324.11 | c.1594C>T | p.Arg532Cys | missense_variant | 17/30 | 1 | NM_016338.5 | P1 | |
IPO11 | ENST00000409296.7 | c.1714C>T | p.Arg572Cys | missense_variant | 17/30 | 2 | |||
IPO11 | ENST00000424533.5 | c.1594C>T | p.Arg532Cys | missense_variant, NMD_transcript_variant | 17/29 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000659 AC: 1AN: 151842Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000687 AC: 9AN: 1309252Hom.: 0 Cov.: 24 AF XY: 0.00000458 AC XY: 3AN XY: 654864
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GnomAD4 genome AF: 0.00000659 AC: 1AN: 151842Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74148
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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 | Jul 05, 2023 | The c.1714C>T (p.R572C) alteration is located in exon 17 (coding exon 17) of the IPO11 gene. This alteration results from a C to T substitution at nucleotide position 1714, causing the arginine (R) at amino acid position 572 to be replaced by a cysteine (C). 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
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Loss of loop (P = 0.0804);.;
MVP
MPC
0.32
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
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