dbSNP rs626716: IPO5:p.Leu259Leu (chr13-97992999-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4BP7BA1

The NM_002271.6(IPO5):c.777A>G(p.Leu259Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0574 in 1,613,432 control chromosomes in the GnomAD database, including 4,914 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 0.075 ( 694 hom., cov: 33)

Exomes 𝑓: 0.056 ( 4220 hom. )

Consequence

IPO5
NM_002271.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.275

Publications

16 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.283).

BP7

Synonymous conserved (PhyloP=0.275 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO5	NM_002271.6 link	c.777A>G	p.Leu259Leu	synonymous_variant	Exon 10 of 29	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.777A>G	p.Leu259Leu	synonymous_variant	Exon 10 of 29		NM_002271.6	ENSP00000499125.1		O00410-1

Frequencies

GnomAD3 genomes

AF:

0.0750

AC:

11414

AN:

152112

Hom.:

693

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.135

Gnomad AMR

AF:

0.0465

Gnomad ASJ

AF:

0.0631

Gnomad EAS

AF:

0.332

Gnomad SAS

AF:

0.160

Gnomad FIN

AF:

0.0415

Gnomad MID

AF:

0.0605

Gnomad NFE

AF:

0.0395

Gnomad OTH

AF:

0.0684

GnomAD2 exomes

AF:

0.0790

AC:

19842

AN:

251272

AF XY:

0.0803

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.0280

Gnomad ASJ exome

AF:

0.0632

Gnomad EAS exome

AF:

0.331

Gnomad FIN exome

AF:

0.0407

Gnomad NFE exome

AF:

0.0420

Gnomad OTH exome

AF:

0.0665

GnomAD4 exome

AF:

0.0556

AC:

81254

AN:

1461202

Hom.:

4220

Cov.:

AF XY:

0.0580

AC XY:

42129

AN XY:

726812

show subpopulations

African (AFR)

AF:

0.113

AC:

3765

AN:

33460

American (AMR)

AF:

0.0309

AC:

1380

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0625

AC:

1634

AN:

26126

East Asian (EAS)

AF:

0.287

AC:

11380

AN:

39666

South Asian (SAS)

AF:

0.138

AC:

11881

AN:

86182

European-Finnish (FIN)

AF:

0.0432

AC:

2308

AN:

53416

Middle Eastern (MID)

AF:

0.0674

AC:

389

AN:

5768

European-Non Finnish (NFE)

AF:

0.0397

AC:

44140

AN:

1111514

Other (OTH)

AF:

0.0725

AC:

4377

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

3523

7046

10568

14091

17614

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0751

AC:

11427

AN:

152230

Hom.:

694

Cov.:

AF XY:

0.0772

AC XY:

5744

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.111

AC:

4590

AN:

41520

American (AMR)

AF:

0.0465

AC:

711

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0631

AC:

219

AN:

3468

East Asian (EAS)

AF:

0.331

AC:

1716

AN:

5180

South Asian (SAS)

AF:

0.161

AC:

775

AN:

4822

European-Finnish (FIN)

AF:

0.0415

AC:

440

AN:

10604

Middle Eastern (MID)

AF:

0.0651

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0394

AC:

2683

AN:

68024

Other (OTH)

AF:

0.0715

AC:

151

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

514

1028

1543

2057

2571

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0539

Hom.:

1052

Bravo

AF:

0.0774

Asia WGS

AF:

0.232

AC:

804

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

6.4

(source)

DANN

Benign

0.73

PhyloP100

0.28

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=92/8

polymorphism (auto)

(source)

Splicing

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

Publications

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rs626716

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