chr13-97990441-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_002271.6(IPO5):c.573G>A(p.Thr191Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000961 in 1,596,650 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00091 ( 23 hom. )

Consequence

IPO5
NM_002271.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.719

Publications

3 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.027).

BP6

Variant 13-97990441-G-A is Benign according to our data. Variant chr13-97990441-G-A is described in ClinVar as Benign. ClinVar VariationId is 771466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.719 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.000906 (1308/1444344) while in subpopulation EAS AF = 0.0177 (701/39556). AF 95% confidence interval is 0.0166. There are 23 homozygotes in GnomAdExome4. There are 591 alleles in the male GnomAdExome4 subpopulation. Median coverage is 29. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002271.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPO5	NM_002271.6	MANE Select	c.573G>A	p.Thr191Thr	synonymous	Exon 9 of 29	NP_002262.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IPO5	ENST00000651721.2	MANE Select	c.573G>A	p.Thr191Thr	synonymous	Exon 9 of 29	ENSP00000499125.1	O00410-1
IPO5	ENST00000261574.10	TSL:1	c.627G>A	p.Thr209Thr	synonymous	Exon 9 of 29	ENSP00000261574.5	O00410-3
IPO5	ENST00000490680.5	TSL:1	c.573G>A	p.Thr191Thr	synonymous	Exon 6 of 26	ENSP00000418393.1	O00410-1

Frequencies

GnomAD3 genomes

AF:

0.00148

AC:

225

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00870

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.0146

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00265

AC:

629

AN:

237778

AF XY:

0.00208

show subpopulations

Gnomad AFR exome

AF:

0.000249

Gnomad AMR exome

AF:

0.0116

Gnomad ASJ exome

AF:

0.000521

Gnomad EAS exome

AF:

0.0142

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000544

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.000906

AC:

1308

AN:

1444344

Hom.:

Cov.:

AF XY:

0.000823

AC XY:

591

AN XY:

718210

show subpopulations

African (AFR)

AF:

0.000154

AC:

AN:

32556

American (AMR)

AF:

0.0117

AC:

473

AN:

40528

Ashkenazi Jewish (ASJ)

AF:

0.000389

AC:

AN:

25722

East Asian (EAS)

AF:

0.0177

AC:

701

AN:

39556

South Asian (SAS)

AF:

0.000621

AC:

AN:

82158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52816

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.0000217

AC:

AN:

1105406

Other (OTH)

AF:

0.000735

AC:

AN:

59860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

120

180

240

300

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.00148

AC:

226

AN:

152306

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

124

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.0000962

AC:

AN:

41572

American (AMR)

AF:

0.00869

AC:

133

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.0148

AC:

AN:

5196

South Asian (SAS)

AF:

0.00104

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68014

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000244

Hom.:

Bravo

AF:

0.00188

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.4

(source)

DANN

Benign

0.82

PhyloP100

-0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over