Genetic Variant IPO5:c.364+64T>A (chr13-97985677-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002271.6(IPO5):c.364+64T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,063,980 control chromosomes in the GnomAD database, including 107,490 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.33 ( 10375 hom., cov: 30)

Exomes 𝑓: 0.45 ( 97115 hom. )

Consequence

IPO5
NM_002271.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.218

Publications

1 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO5	NM_002271.6 link	c.364+64T>A		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+64T>A		intron_variant	Intron 6 of 28		NM_002271.6	ENSP00000499125.1		O00410-1

Frequencies

GnomAD3 genomes

AF:

0.333

AC:

49306

AN:

147994

Hom.:

10376

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0902

Gnomad AMI

AF:

0.455

Gnomad AMR

AF:

0.312

Gnomad ASJ

AF:

0.372

Gnomad EAS

AF:

0.0232

Gnomad SAS

AF:

0.336

Gnomad FIN

AF:

0.477

Gnomad MID

AF:

0.315

Gnomad NFE

AF:

0.475

Gnomad OTH

AF:

0.315

GnomAD4 exome

AF:

0.448

AC:

410181

AN:

915876

Hom.:

97115

AF XY:

0.448

AC XY:

212222

AN XY:

474206

show subpopulations

African (AFR)

AF:

0.0852

AC:

1566

AN:

18386

American (AMR)

AF:

0.280

AC:

9517

AN:

34046

Ashkenazi Jewish (ASJ)

AF:

0.390

AC:

8218

AN:

21072

East Asian (EAS)

AF:

0.0154

AC:

545

AN:

35310

South Asian (SAS)

AF:

0.370

AC:

24529

AN:

66328

European-Finnish (FIN)

AF:

0.478

AC:

24037

AN:

50290

Middle Eastern (MID)

AF:

0.361

AC:

1320

AN:

3654

European-Non Finnish (NFE)

AF:

0.501

AC:

323532

AN:

645642

Other (OTH)

AF:

0.411

AC:

16917

AN:

41148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

Heterozygous variant carriers

10735

21470

32205

42940

53675

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7062

14124

21186

28248

35310

<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:

0.333

AC:

49295

AN:

148104

Hom.:

10375

Cov.:

AF XY:

0.330

AC XY:

23868

AN XY:

72262

show subpopulations

African (AFR)

AF:

0.0901

AC:

3478

AN:

38604

American (AMR)

AF:

0.312

AC:

4701

AN:

15078

Ashkenazi Jewish (ASJ)

AF:

0.372

AC:

1282

AN:

3450

East Asian (EAS)

AF:

0.0228

AC:

116

AN:

5082

South Asian (SAS)

AF:

0.336

AC:

1593

AN:

4744

European-Finnish (FIN)

AF:

0.477

AC:

4861

AN:

10200

Middle Eastern (MID)

AF:

0.310

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.475

AC:

32114

AN:

67676

Other (OTH)

AF:

0.313

AC:

649

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

1474

2948

4421

5895

7369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

484

968

1452

1936

2420

<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:

0.396

Hom.:

1659

Bravo

AF:

0.302

Asia WGS

AF:

0.167

AC:

579

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.8

(source)

DANN

Benign

0.44

PhyloP100

0.22

Mutation Taster

=100/0

polymorphism (auto)

(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