13-98002421-G-A

Position:

• chr13-98002421-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002271.6(IPO5):​c.1109-46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,589,462 control chromosomes in the GnomAD database, including 9,829 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 0.078 (638 hom., cov: 33)
  • Exomes 𝑓: 0.11 (9191 hom.)
• Consequence: IPO5 NM_002271.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IPO5	NM_002271.6	c.1109-46G>A		intron_variant		ENST00000651721.2	NP_002262.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IPO5	ENST00000651721.2	c.1109-46G>A		intron_variant			NM_002271.6	ENSP00000499125.1

Frequencies

GnomAD3 genomes AF: 0.0781 AC: 11879 AN: 152156 Hom.: 636 Cov.: 33

Gnomad AFR AF: 0.0191

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0569

Gnomad ASJ AF: 0.0619

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.0813

GnomAD3 exomes AF: 0.0820 AC: 20027 AN: 244334 Hom.: 1176 AF XY: 0.0823 AC XY: 10887 AN XY: 132208

Gnomad AFR exome AF: 0.0178

Gnomad AMR exome AF: 0.0454

Gnomad ASJ exome AF: 0.0573

Gnomad EAS exome AF: 0.000275

Gnomad SAS exome AF: 0.0308

Gnomad FIN exome AF: 0.145

Gnomad NFE exome AF: 0.119

Gnomad OTH exome AF: 0.0853

GnomAD4 exome AF: 0.105 AC: 151431 AN: 1437188 Hom.: 9191 Cov.: 28 AF XY: 0.103 AC XY: 73645 AN XY: 715862

Gnomad4 AFR exome AF: 0.0147

Gnomad4 AMR exome AF: 0.0464

Gnomad4 ASJ exome AF: 0.0587

Gnomad4 EAS exome AF: 0.000152

Gnomad4 SAS exome AF: 0.0298

Gnomad4 FIN exome AF: 0.140

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.0919

GnomAD4 genome AF: 0.0780 AC: 11881 AN: 152274 Hom.: 638 Cov.: 33 AF XY: 0.0750 AC XY: 5581 AN XY: 74460

Gnomad4 AFR AF: 0.0191

Gnomad4 AMR AF: 0.0568

Gnomad4 ASJ AF: 0.0619

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0325

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.0804

Alfa AF: 0.0921 Hom.: 146

Bravo AF: 0.0695

Asia WGS AF: 0.0200 AC: 72 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.95
DANN	Benign	0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs61970445; hg19: chr13-98654675;