Genetic Variant IPO5:c.*1875A>G (chr13-98023697-A-G) – 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.*1875A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 152,034 control chromosomes in the GnomAD database, including 11,382 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 ( 11382 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IPO5
NM_002271.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.894

Publications

5 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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO5	NM_002271.6 link	c.*1875A>G		3_prime_UTR_variant	Exon 29 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.*1875A>G		3_prime_UTR_variant	Exon 29 of 29		NM_002271.6	ENSP00000499125.1		O00410-1
IPO5	ENST00000261574.10 link	c.*1875A>G		3_prime_UTR_variant	Exon 29 of 29	1		ENSP00000261574.5		O00410-3

Frequencies

GnomAD3 genomes

AF:

0.364

AC:

55264

AN:

151916

Hom.:

11380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.206

Gnomad AMI

AF:

0.456

Gnomad AMR

AF:

0.328

Gnomad ASJ

AF:

0.372

Gnomad EAS

AF:

0.0227

Gnomad SAS

AF:

0.335

Gnomad FIN

AF:

0.478

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.477

Gnomad OTH

AF:

0.340

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.364

AC:

55266

AN:

152034

Hom.:

11382

Cov.:

AF XY:

0.360

AC XY:

26779

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.206

AC:

8550

AN:

41498

American (AMR)

AF:

0.327

AC:

5002

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.372

AC:

1292

AN:

3472

East Asian (EAS)

AF:

0.0224

AC:

116

AN:

5182

South Asian (SAS)

AF:

0.335

AC:

1610

AN:

4812

European-Finnish (FIN)

AF:

0.478

AC:

5042

AN:

10540

Middle Eastern (MID)

AF:

0.333

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.477

AC:

32431

AN:

67938

Other (OTH)

AF:

0.336

AC:

710

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1692

3384

5077

6769

8461

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.424

Hom.:

22404

Bravo

AF:

0.344

Asia WGS

AF:

0.179

AC:

621

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.52

(source)

DANN

Benign

0.35

PhyloP100

-0.89

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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chr13-98023697-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over