Genetic Variant IPO13:p.Asp415Asp (chr1-43956950-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

The NM_014652.4(IPO13):c.1245C>T(p.Asp415Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0344 in 1,614,084 control chromosomes in the GnomAD database, including 1,069 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 0.027 ( 67 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1002 hom. )

Consequence

IPO13
NM_014652.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0620

Publications

5 publications found

Variant links:

Genes affected

IPO13 (HGNC:16853): (importin 13) This gene encodes a member of the importin-beta family of nuclear transport proteins. The encoded protein mediates the import of specific cargo proteins from the cytoplasm to the nucleus and is dependent on the Ras-related nuclear protein-GTPase system. The encoded protein is also involved in nuclear export of the eukaryotic translation initiation factor 1A.[provided by RefSeq, Mar 2009]

IPO13 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP7

Synonymous conserved (PhyloP=-0.062 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0272 (4139/152344) while in subpopulation NFE AF = 0.0395 (2690/68034). AF 95% confidence interval is 0.0383. There are 67 homozygotes in GnomAd4. There are 1958 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 4139 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
IPO13	NM_014652.4 link	c.1245C>T	p.Asp415Asp	synonymous_variant	Exon 5 of 20	ENST00000372343.8	NP_055467.3
IPO13	XM_024451069.2 link	c.342C>T	p.Asp114Asp	synonymous_variant	Exon 4 of 19		XP_024306837.1
IPO13	XM_024451070.2 link	c.342C>T	p.Asp114Asp	synonymous_variant	Exon 4 of 19		XP_024306838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
IPO13	ENST00000372343.8 link	c.1245C>T	p.Asp415Asp	synonymous_variant	Exon 5 of 20	1	NM_014652.4	ENSP00000361418.3
IPO13	ENST00000492152.5 link	n.691C>T		non_coding_transcript_exon_variant	Exon 4 of 6	3
IPO13	ENST00000480902.1 link	n.-159C>T		upstream_gene_variant		3
IPO13	ENST00000489773.5 link	n.*106C>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0272

AC:

4142

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00646

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0320

Gnomad ASJ

AF:

0.0294

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0329

Gnomad FIN

AF:

0.0328

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0395

Gnomad OTH

AF:

0.0296

GnomAD2 exomes

AF:

0.0287

AC:

7198

AN:

251110

AF XY:

0.0297

show subpopulations

Gnomad AFR exome

AF:

0.00653

Gnomad AMR exome

AF:

0.0175

Gnomad ASJ exome

AF:

0.0249

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0332

Gnomad NFE exome

AF:

0.0393

Gnomad OTH exome

AF:

0.0293

GnomAD4 exome

AF:

0.0352

AC:

51381

AN:

1461740

Hom.:

1002

Cov.:

AF XY:

0.0351

AC XY:

25515

AN XY:

727178

show subpopulations

African (AFR)

AF:

0.00580

AC:

194

AN:

33476

American (AMR)

AF:

0.0174

AC:

777

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.0259

AC:

678

AN:

26132

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0309

AC:

2661

AN:

86248

European-Finnish (FIN)

AF:

0.0349

AC:

1865

AN:

53400

Middle Eastern (MID)

AF:

0.0363

AC:

209

AN:

5756

European-Non Finnish (NFE)

AF:

0.0387

AC:

43047

AN:

1111932

Other (OTH)

AF:

0.0323

AC:

1948

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

2558

5116

7674

10232

12790

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1584

3168

4752

6336

7920

<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:

0.0272

AC:

4139

AN:

152344

Hom.:

Cov.:

AF XY:

0.0263

AC XY:

1958

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00645

AC:

268

AN:

41582

American (AMR)

AF:

0.0319

AC:

488

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0294

AC:

102

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.0327

AC:

158

AN:

4830

European-Finnish (FIN)

AF:

0.0328

AC:

348

AN:

10608

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0395

AC:

2690

AN:

68034

Other (OTH)

AF:

0.0293

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

219

439

658

878

1097

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.0306

Hom.:

Bravo

AF:

0.0255

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0429

EpiControl

AF:

0.0373

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

6.7

(source)

DANN

Benign

0.51

PhyloP100

-0.062

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=93/7

polymorphism (auto)

(source)

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

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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