13-97988969-G-GT

Position:

• chr13-97988969-G-GT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002271.6(IPO5):​c.365-90dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 653,882 control chromosomes in the GnomAD database, including 3,303 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.075 (710 hom., cov: 32)
  • Exomes 𝑓: 0.067 (2593 hom.)
• Consequence: IPO5 NM_002271.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IPO5	NM_002271.6	c.365-90dupT		intron_variant		ENST00000651721.2	NP_002262.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IPO5	ENST00000651721.2	c.365-90dupT		intron_variant			NM_002271.6	ENSP00000499125.1

Frequencies

GnomAD3 genomes AF: 0.0753 AC: 11430 AN: 151792 Hom.: 707 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0462

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0416

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0395

Gnomad OTH AF: 0.0689

GnomAD4 exome AF: 0.0674 AC: 33823 AN: 501974 Hom.: 2593 AF XY: 0.0688 AC XY: 18571 AN XY: 269896

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.0325

Gnomad4 ASJ exome AF: 0.0622

Gnomad4 EAS exome AF: 0.314

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.0419

Gnomad4 NFE exome AF: 0.0390

Gnomad4 OTH exome AF: 0.0722

GnomAD4 genome AF: 0.0754 AC: 11447 AN: 151908 Hom.: 710 Cov.: 32 AF XY: 0.0776 AC XY: 5761 AN XY: 74254

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.0461

Gnomad4 ASJ AF: 0.0657

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.0416

Gnomad4 NFE AF: 0.0395

Gnomad4 OTH AF: 0.0734

Alfa AF: 0.0506 Hom.: 3

Asia WGS AF: 0.234 AC: 812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3832890; hg19: chr13-98641223;