Genetic Variant NM_002271.6:c.-5+103A>C (chr13-97969933-A-C) – 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.-5+103A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 817,148 control chromosomes in the GnomAD database, including 75,824 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 0.36 ( 11253 hom., cov: 32)

Exomes 𝑓: 0.43 ( 64571 hom. )

Consequence

IPO5
NM_002271.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.597

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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO5	NM_002271.6 link	c.-5+103A>C		intron_variant	Intron 3 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.-5+103A>C		intron_variant	Intron 3 of 28		NM_002271.6	ENSP00000499125.1		O00410-1

Frequencies

GnomAD3 genomes

AF:

0.362

AC:

54896

AN:

151766

Hom.:

11253

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.323

Gnomad ASJ

AF:

0.373

Gnomad EAS

AF:

0.0226

Gnomad SAS

AF:

0.335

Gnomad FIN

AF:

0.478

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.476

Gnomad OTH

AF:

0.341

GnomAD4 exome

AF:

0.425

AC:

283022

AN:

665264

Hom.:

64571

Cov.:

AF XY:

0.426

AC XY:

148825

AN XY:

349294

show subpopulations

African (AFR)

AF:

0.195

AC:

3006

AN:

15442

American (AMR)

AF:

0.282

AC:

7898

AN:

28016

Ashkenazi Jewish (ASJ)

AF:

0.378

AC:

6657

AN:

17608

East Asian (EAS)

AF:

0.0149

AC:

468

AN:

31340

South Asian (SAS)

AF:

0.363

AC:

19947

AN:

55026

European-Finnish (FIN)

AF:

0.472

AC:

23323

AN:

49392

Middle Eastern (MID)

AF:

0.371

AC:

1111

AN:

2992

European-Non Finnish (NFE)

AF:

0.479

AC:

207194

AN:

432310

Other (OTH)

AF:

0.405

AC:

13418

AN:

33138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

7564

15129

22693

30258

37822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3020

6040

9060

12080

15100

<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:

0.361

AC:

54893

AN:

151884

Hom.:

11253

Cov.:

AF XY:

0.358

AC XY:

26606

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.201

AC:

8337

AN:

41422

American (AMR)

AF:

0.323

AC:

4932

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

1294

AN:

3470

East Asian (EAS)

AF:

0.0223

AC:

114

AN:

5110

South Asian (SAS)

AF:

0.335

AC:

1609

AN:

4806

European-Finnish (FIN)

AF:

0.478

AC:

5055

AN:

10572

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.476

AC:

32330

AN:

67912

Other (OTH)

AF:

0.337

AC:

710

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1681

3362

5044

6725

8406

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<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:

0.307

Hom.:

902

Bravo

AF:

0.341

Asia WGS

AF:

0.177

AC:

615

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

3.3

(source)

DANN

Benign

0.59

PhyloP100

0.60

PromoterAI

-0.018

Neutral

(source)

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