Variant rs626716 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

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

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 made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

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/exons	MANE	Protein	UniProt
IPO5	NM_002271.6 linkuse as main transcript	c.777A>G	p.Leu259Leu	synonymous_variant	10/29	ENST00000651721.2	NP_002262.4	O00410-1Q9BVS9B3KWG6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IPO5	ENST00000651721.2 linkuse as main transcript	c.777A>G	p.Leu259Leu	synonymous_variant	10/29		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

GnomAD3 exomes

AF:

0.0790

AC:

19842

AN:

251272

Hom.:

1636

AF XY:

0.0803

AC XY:

10908

AN XY:

135790

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 SAS exome

AF:

0.140

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

Gnomad4 AFR exome

AF:

0.113

Gnomad4 AMR exome

AF:

0.0309

Gnomad4 ASJ exome

AF:

0.0625

Gnomad4 EAS exome

AF:

0.287

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.0432

Gnomad4 NFE exome

AF:

0.0397

Gnomad4 OTH exome

AF:

0.0725

GnomAD4 genome

AF:

0.0751

AC:

11427

AN:

152230

Hom.:

694

Cov.:

AF XY:

0.0772

AC XY:

5744

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.0465

Gnomad4 ASJ

AF:

0.0631

Gnomad4 EAS

AF:

0.331

Gnomad4 SAS

AF:

0.161

Gnomad4 FIN

AF:

0.0415

Gnomad4 NFE

AF:

0.0394

Gnomad4 OTH

AF:

0.0715

Alfa

AF:

0.0508

Hom.:

603

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

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over