12-30637041-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_006390.4(IPO8):c.2636G>A(p.Arg879Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0114 in 1,613,952 control chromosomes in the GnomAD database, including 129 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0076 ( 4 hom., cov: 32)

Exomes 𝑓: 0.012 ( 125 hom. )

Consequence

IPO8
NM_006390.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.85

Variant links:

Genes affected

IPO8 (HGNC:9853): (importin 8) The importin-alpha/beta complex and the GTPase Ran mediate nuclear import of proteins with a classical nuclear localization signal. The protein encoded by this gene is a member of a class of approximately 20 potential Ran targets that share a sequence motif related to the Ran-binding site of importin-beta. This protein binds to the nuclear pore complex and, along with RanGTP and RANBP1, inhibits the GAP stimulation of the Ran GTPase. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

IPO8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042545497).

BP6

Variant 12-30637041-C-T is Benign according to our data. Variant chr12-30637041-C-T is described in ClinVar as [Benign]. Clinvar id is 1701194.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00759 (1156/152226) while in subpopulation NFE AF = 0.0126 (860/68020). AF 95% confidence interval is 0.0119. There are 4 homozygotes in GnomAd4. There are 524 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO8	NM_006390.4 link	c.2636G>A	p.Arg879Lys	missense_variant	Exon 22 of 25	ENST00000256079.9	NP_006381.2	O15397-1
IPO8	NM_001190995.2 link	c.2021G>A	p.Arg674Lys	missense_variant	Exon 18 of 21		NP_001177924.1	O15397-2
IPO8	XM_017018691.3 link	c.2585G>A	p.Arg862Lys	missense_variant	Exon 22 of 25		XP_016874180.1
IPO8	XM_017018692.2 link	c.2450G>A	p.Arg817Lys	missense_variant	Exon 21 of 24		XP_016874181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IPO8	ENST00000256079.9 link	c.2636G>A	p.Arg879Lys	missense_variant	Exon 22 of 25	1	NM_006390.4	ENSP00000256079.4	O15397-1
IPO8	ENST00000544829.5 link	c.2021G>A	p.Arg674Lys	missense_variant	Exon 18 of 21	2		ENSP00000444520.1	O15397-2
IPO8	ENST00000535598.1 link	c.107G>A	p.Arg36Lys	missense_variant	Exon 1 of 3	3		ENSP00000446232.1	H0YH64

Frequencies

GnomAD3 genomes

AF:

0.00759

AC:

1155

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00244

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00519

Gnomad FIN

AF:

0.00368

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0126

Gnomad OTH

AF:

0.00766

GnomAD2 exomes

AF:

0.00831

AC:

2087

AN:

251102

AF XY:

0.00861

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00408

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00388

Gnomad NFE exome

AF:

0.0137

Gnomad OTH exome

AF:

0.00768

GnomAD4 exome

AF:

0.0118

AC:

17232

AN:

1461726

Hom.:

125

Cov.:

AF XY:

0.0117

AC XY:

8494

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.00188

AC:

AN:

33480

Gnomad4 AMR exome

AF:

0.00465

AC:

208

AN:

44724

Gnomad4 ASJ exome

AF:

0.00134

AC:

AN:

26130

Gnomad4 EAS exome

AF:

0.0000756

AC:

AN:

39686

Gnomad4 SAS exome

AF:

0.00678

AC:

585

AN:

86256

Gnomad4 FIN exome

AF:

0.00468

AC:

250

AN:

53410

Gnomad4 NFE exome

AF:

0.0140

AC:

15513

AN:

1111878

Gnomad4 Remaining exome

AF:

0.00886

AC:

535

AN:

60394

Heterozygous variant carriers

833

1666

2498

3331

4164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

578

1156

1734

2312

2890

<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:

0.00759

AC:

1156

AN:

152226

Hom.:

Cov.:

AF XY:

0.00704

AC XY:

524

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00243

AC:

0.00243221

AN:

0.00243221

Gnomad4 AMR

AF:

0.00530

AC:

0.0052955

AN:

0.0052955

Gnomad4 ASJ

AF:

0.00144

AC:

0.00144425

AN:

0.00144425

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00540

AC:

0.00539867

AN:

0.00539867

Gnomad4 FIN

AF:

0.00368

AC:

0.00367716

AN:

0.00367716

Gnomad4 NFE

AF:

0.0126

AC:

0.0126433

AN:

0.0126433

Gnomad4 OTH

AF:

0.00758

AC:

0.00757576

AN:

0.00757576

Heterozygous variant carriers

113

169

226

282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0115

Hom.:

Bravo

AF:

0.00773

TwinsUK

AF:

0.0143

AC:

ALSPAC

AF:

0.0125

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0134

AC:

115

ExAC

AF:

0.00864

AC:

1049

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

IPO8: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.63

T;T

MetaRNN

Benign

0.0043

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.3

L;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.67

N;N

REVEL

Benign

0.11

Sift

Benign

0.31

T;T

Sift4G

Benign

0.25

T;T

Polyphen

0.10

B;.

Vest4

0.22

MVP

0.42

MPC

0.27

ClinPred

0.019

GERP RS

3.2

Varity_R

0.071

gMVP

0.33

Mutation Taster

=99/1

polymorphism

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over