13-97985663-CTTTTT-CTTT

Position:

• chr13-97985663-CTTTTT-CTTT

Variant summary

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

The NM_002271.6(IPO5):​c.364+63_364+64del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0322 in 896,014 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00070 (0 hom., cov: 0)
  • Exomes 𝑓: 0.038 (2 hom.)
• Consequence: IPO5 NM_002271.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IPO5	NM_002271.6	c.364+63_364+64del		intron_variant		ENST00000651721.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IPO5	ENST00000651721.2	c.364+63_364+64del		intron_variant			NM_002271.6	P1

Frequencies

GnomAD3 genomes AF: 0.000700 AC: 102 AN: 145624 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000345

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000655

Gnomad FIN AF: 0.00227

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000377

Gnomad OTH AF: 0.000498

GnomAD3 exomes AF: 0.0411 AC: 5359 AN: 130350 Hom.: 2 AF XY: 0.0422 AC XY: 3005 AN XY: 71246

Gnomad AFR exome AF: 0.0733

Gnomad AMR exome AF: 0.0340

Gnomad ASJ exome AF: 0.0472

Gnomad EAS exome AF: 0.0195

Gnomad SAS exome AF: 0.0527

Gnomad FIN exome AF: 0.0298

Gnomad NFE exome AF: 0.0410

Gnomad OTH exome AF: 0.0382

GnomAD4 exome AF: 0.0384 AC: 28776 AN: 750336 Hom.: 2 AF XY: 0.0387 AC XY: 15085 AN XY: 389844

Gnomad4 AFR exome AF: 0.0882

Gnomad4 AMR exome AF: 0.0285

Gnomad4 ASJ exome AF: 0.0359

Gnomad4 EAS exome AF: 0.0170

Gnomad4 SAS exome AF: 0.0420

Gnomad4 FIN exome AF: 0.0312

Gnomad4 NFE exome AF: 0.0390

Gnomad4 OTH exome AF: 0.0383

GnomAD4 genome AF: 0.000700 AC: 102 AN: 145678 Hom.: 0 Cov.: 0 AF XY: 0.000722 AC XY: 51 AN XY: 70644

Gnomad4 AFR AF: 0.00118

Gnomad4 AMR AF: 0.000345

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000658

Gnomad4 FIN AF: 0.00227

Gnomad4 NFE AF: 0.000377

Gnomad4 OTH AF: 0.000495

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: rs11366582; hg19: chr13-98637917;