13-98006356-ATTTTTTTTTTTTTTTTTTTTTTTT-ATTTTTTTT

Variant names:

• chr13-98006356-ATTTTTTTTTTTTTTTT-A
• rs568589408
• NM_002271.6:c.1716+29_1716+44delTTTTTTTTTTTTTTTT

Variant summary

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

The NM_002271.6(IPO5):​c.1716+29_1716+44delTTTTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.057 in 491,976 control chromosomes in the GnomAD database, including 834 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.075 (255 hom., cov: 0)
  • Exomes 𝑓: 0.057 (834 hom.)
  • Failed GnomAD Quality Control
• Consequence: IPO5 NM_002271.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

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 (EAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO5	NM_002271.6	c.1716+29_1716+44delTTTTTTTTTTTTTTTT		intron_variant	Intron 17 of 28	ENST00000651721.2	NP_002262.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPO5	ENST00000651721.2	c.1716+9_1716+24delTTTTTTTTTTTTTTTT		intron_variant	Intron 17 of 28		NM_002271.6	ENSP00000499125.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 4712 AN: 62848 Hom.: 256 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0247

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.0666

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.0563

Gnomad MID AF: 0.109

Gnomad NFE AF: 0.0591

Gnomad OTH AF: 0.0841

GnomAD4 exome AF: 0.0570 AC: 28032 AN: 491976 Hom.: 834 AF XY: 0.0581 AC XY: 15117 AN XY: 259980

Gnomad4 AFR exome AF: 0.0226

Gnomad4 AMR exome AF: 0.0227

Gnomad4 ASJ exome AF: 0.0608

Gnomad4 EAS exome AF: 0.282

Gnomad4 SAS exome AF: 0.0999

Gnomad4 FIN exome AF: 0.0280

Gnomad4 NFE exome AF: 0.0425

Gnomad4 OTH exome AF: 0.0721

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0748 AC: 4700 AN: 62856 Hom.: 255 Cov.: 0 AF XY: 0.0787 AC XY: 2217 AN XY: 28160

Gnomad4 AFR AF: 0.0246

Gnomad4 AMR AF: 0.0665

Gnomad4 ASJ AF: 0.0867

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.0563

Gnomad4 NFE AF: 0.0590

Gnomad4 OTH AF: 0.0867

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: rs568589408; hg19: chr13-98658610;