chr1-43949668-T-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_014652.4(IPO13):c.336T>G(p.Phe112Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000514 in 1,614,250 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000051 ( 0 hom. )
Consequence
IPO13
NM_014652.4 missense
NM_014652.4 missense
Scores
2
10
7
Clinical Significance
Conservation
PhyloP100: 0.0200
Genes affected
IPO13 (HGNC:16853): (importin 13) This gene encodes a member of the importin-beta family of nuclear transport proteins. The encoded protein mediates the import of specific cargo proteins from the cytoplasm to the nucleus and is dependent on the Ras-related nuclear protein-GTPase system. The encoded protein is also involved in nuclear export of the eukaryotic translation initiation factor 1A.[provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, IPO13
BS2
?
High AC in GnomAd at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IPO13 | NM_014652.4 | c.336T>G | p.Phe112Leu | missense_variant | 2/20 | ENST00000372343.8 | |
IPO13 | XM_024451069.2 | c.-83+1984T>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IPO13 | ENST00000372343.8 | c.336T>G | p.Phe112Leu | missense_variant | 2/20 | 1 | NM_014652.4 | P1 | |
IPO13 | ENST00000489773.5 | n.116-418T>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000525 AC: 8AN: 152242Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251468Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135904
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GnomAD4 exome AF: 0.0000513 AC: 75AN: 1461890Hom.: 0 Cov.: 31 AF XY: 0.0000481 AC XY: 35AN XY: 727246
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GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152360Hom.: 0 Cov.: 33 AF XY: 0.0000805 AC XY: 6AN XY: 74508
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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 09, 2022 | The c.336T>G (p.F112L) alteration is located in exon 2 (coding exon 2) of the IPO13 gene. This alteration results from a T to G substitution at nucleotide position 336, causing the phenylalanine (F) at amino acid position 112 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Uncertain
DEOGEN2
Uncertain
D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Pathogenic
D
Polyphen
P
Vest4
MutPred
Gain of MoRF binding (P = 0.1144);
MVP
MPC
ClinPred
T
GERP RS
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