Variant 1-43956346-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014652.4(IPO13):c.848T>C(p.Ile283Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

IPO13
NM_014652.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.22

Variant links:

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]

IPO13 links:

IPO13 (HGNC:):

IPO13 links:

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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	Protein	UniProt
IPO13	NM_014652.4 linkuse as main transcript	c.848T>C	p.Ile283Thr	missense_variant	3/20	ENST00000372343.8	NP_055467.3	O94829
IPO13	XM_024451069.2 linkuse as main transcript	c.-56T>C		5_prime_UTR_variant	2/19		XP_024306837.1
IPO13	XM_024451070.2 linkuse as main transcript	c.-56T>C		5_prime_UTR_variant	2/19		XP_024306838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IPO13	ENST00000372343.8 linkuse as main transcript	c.848T>C	p.Ile283Thr	missense_variant	3/20	1	NM_014652.4	ENSP00000361418.3	O94829
IPO13	ENST00000489773.5 linkuse as main transcript	n.210T>C		non_coding_transcript_exon_variant	3/5	3
IPO13	ENST00000492152.5 linkuse as main transcript	n.294T>C		non_coding_transcript_exon_variant	2/6	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Oct 21, 2024

The c.848T>C (p.I283T) alteration is located in exon 3 (coding exon 3) of the IPO13 gene. This alteration results from a T to C substitution at nucleotide position 848, causing the isoleucine (I) at amino acid position 283 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Uncertain

0.090

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.33

Eigen

Benign

0.069

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.0073

MetaRNN

Uncertain

0.45

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.75

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-2.0

REVEL

Benign

0.16

Sift

Uncertain

0.013

Sift4G

Uncertain

0.013

Polyphen

0.080

Vest4

0.72

MutPred

0.57

Loss of stability (P = 0.0016);

MVP

0.29

MPC

0.44

ClinPred

0.87

GERP RS

4.7

Varity_R

0.39

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over