Genetic Variant NM_002271.6:c.364+64dupT (chr13-97985663-C-CT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_002271.6(IPO5):c.364+64dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 0)

Exomes 𝑓: 0.031 ( 0 hom. )

Consequence

IPO5
NM_002271.6 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.76

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: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO5	NM_002271.6 link	c.364+64dupT		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+50_364+51insT		intron_variant	Intron 6 of 28		NM_002271.6	ENSP00000499125.1		O00410-1

Frequencies

GnomAD3 genomes

AF:

0.00223

AC:

325

AN:

145810

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00621

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.000296

Gnomad EAS

AF:

0.00102

Gnomad SAS

AF:

0.00109

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000407

Gnomad OTH

AF:

0.00348

GnomAD2 exomes

AF:

0.0232

AC:

3019

AN:

130350

AF XY:

0.0219

show subpopulations

Gnomad AFR exome

AF:

0.0149

Gnomad AMR exome

AF:

0.0406

Gnomad ASJ exome

AF:

0.0221

Gnomad EAS exome

AF:

0.0680

Gnomad FIN exome

AF:

0.0137

Gnomad NFE exome

AF:

0.0146

Gnomad OTH exome

AF:

0.0296

GnomAD4 exome

AF:

0.0310

AC:

24060

AN:

775806

Hom.:

Cov.:

AF XY:

0.0308

AC XY:

12413

AN XY:

403396

show subpopulations

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

African (AFR)

AF:

0.0215

AC:

362

AN:

16810

American (AMR)

AF:

0.0417

AC:

1196

AN:

28710

Ashkenazi Jewish (ASJ)

AF:

0.0359

AC:

658

AN:

18348

East Asian (EAS)

AF:

0.0638

AC:

2057

AN:

32242

South Asian (SAS)

AF:

0.0358

AC:

2056

AN:

57510

European-Finnish (FIN)

AF:

0.0228

AC:

998

AN:

43866

Middle Eastern (MID)

AF:

0.0274

AC:

AN:

3290

European-Non Finnish (NFE)

AF:

0.0288

AC:

15521

AN:

539210

Other (OTH)

AF:

0.0313

AC:

1122

AN:

35820

⚠️ 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: 0.287

Heterozygous variant carriers

1999

3998

5998

7997

9996

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

466

932

1398

1864

2330

<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:

0.00222

AC:

324

AN:

145864

Hom.:

Cov.:

AF XY:

0.00232

AC XY:

164

AN XY:

70764

show subpopulations

African (AFR)

AF:

0.00617

AC:

245

AN:

39734

American (AMR)

AF:

0.00138

AC:

AN:

14514

Ashkenazi Jewish (ASJ)

AF:

0.000296

AC:

AN:

3382

East Asian (EAS)

AF:

0.00103

AC:

AN:

4876

South Asian (SAS)

AF:

0.00110

AC:

AN:

4558

European-Finnish (FIN)

AF:

0.00151

AC:

AN:

9300

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.000407

AC:

AN:

66322

Other (OTH)

AF:

0.00346

AC:

AN:

2026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00

Hom.:

584

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.8

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over