Genetic Variant IPO5:c.364+62_364+64delTTT (chr13-97985663-CTTT-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002271.6(IPO5):c.364+62_364+64delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000297 in 930,176 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00035 ( 1 hom. )

Consequence

IPO5
NM_002271.6 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0980

Publications

0 publications found

Variant links:

Genes affected

IPO5 (HGNC:6402): (importin 5) Nucleocytoplasmic transport, a signal- and energy-dependent process, takes place through nuclear pore complexes embedded in the nuclear envelope. The import of proteins containing a nuclear localization signal (NLS) requires the NLS import receptor, a heterodimer of importin alpha and beta subunits also known as karyopherins. Importin alpha binds the NLS-containing cargo in the cytoplasm and importin beta docks the complex at the cytoplasmic side of the nuclear pore complex. In the presence of nucleoside triphosphates and the small GTP binding protein Ran, the complex moves into the nuclear pore complex and the importin subunits dissociate. Importin alpha enters the nucleoplasm with its passenger protein and importin beta remains at the pore. Interactions between importin beta and the FG repeats of nucleoporins are essential in translocation through the pore complex. The protein encoded by this gene is a member of the importin beta family. [provided by RefSeq, Jul 2008]

IPO5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO5	NM_002271.6 link	c.364+62_364+64delTTT		intron_variant	Intron 6 of 28	ENST00000651721.2	NP_002262.4	O00410-1Q9BVS9B3KWG6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPO5	ENST00000651721.2 link	c.364+51_364+53delTTT		intron_variant	Intron 6 of 28		NM_002271.6	ENSP00000499125.1		O00410-1

Frequencies

GnomAD3 genomes

AF:

0.00000686

AC:

AN:

145810

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000252

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000422

AC:

AN:

130350

AF XY:

0.000435

show subpopulations

Gnomad AFR exome

AF:

0.000933

Gnomad AMR exome

AF:

0.000243

Gnomad ASJ exome

AF:

0.000385

Gnomad EAS exome

AF:

0.000226

Gnomad FIN exome

AF:

0.000230

Gnomad NFE exome

AF:

0.000458

Gnomad OTH exome

AF:

0.000319

GnomAD4 exome

AF:

0.000351

AC:

275

AN:

784366

Hom.:

AF XY:

0.000314

AC XY:

128

AN XY:

407844

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00190

AC:

AN:

16828

American (AMR)

AF:

0.000137

AC:

AN:

29132

Ashkenazi Jewish (ASJ)

AF:

0.000107

AC:

AN:

18652

East Asian (EAS)

AF:

0.0000597

AC:

AN:

33524

South Asian (SAS)

AF:

0.000326

AC:

AN:

58288

European-Finnish (FIN)

AF:

0.0000899

AC:

AN:

44506

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3328

European-Non Finnish (NFE)

AF:

0.000375

AC:

204

AN:

543846

Other (OTH)

AF:

0.000221

AC:

AN:

36262

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.252

Heterozygous variant carriers

116

155

194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000686

AC:

AN:

145810

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

70698

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000252

AC:

AN:

39628

American (AMR)

AF:

0.00

AC:

AN:

14500

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3386

East Asian (EAS)

AF:

0.00

AC:

AN:

4890

South Asian (SAS)

AF:

0.00

AC:

AN:

4582

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66330

Other (OTH)

AF:

0.00

AC:

AN:

2012

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.098

Splicing

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

Publications

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13-97985663-CTTTTT-CTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over