13-97985663-CTTTTT-CTT

Position:

• chr13-97985663-CTTTTT-CTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002271.6(IPO5):​c.364+62_364+64del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000297 in 930,176 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000069 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00035 (1 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IPO5	NM_002271.6	c.364+62_364+64del		intron_variant		ENST00000651721.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IPO5	ENST00000651721.2	c.364+62_364+64del		intron_variant			NM_002271.6	P1

Frequencies

GnomAD3 genomes AF: 0.00000686 AC: 1 AN: 145810 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000252

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000422 AC: 55 AN: 130350 Hom.: 0 AF XY: 0.000435 AC XY: 31 AN XY: 71246

Gnomad AFR exome AF: 0.000933

Gnomad AMR exome AF: 0.000243

Gnomad ASJ exome AF: 0.000385

Gnomad EAS exome AF: 0.000226

Gnomad SAS exome AF: 0.000501

Gnomad FIN exome AF: 0.000230

Gnomad NFE exome AF: 0.000458

Gnomad OTH exome AF: 0.000319

GnomAD4 exome AF: 0.000351 AC: 275 AN: 784366 Hom.: 1 AF XY: 0.000314 AC XY: 128 AN XY: 407844

Gnomad4 AFR exome AF: 0.00190

Gnomad4 AMR exome AF: 0.000137

Gnomad4 ASJ exome AF: 0.000107

Gnomad4 EAS exome AF: 0.0000597

Gnomad4 SAS exome AF: 0.000326

Gnomad4 FIN exome AF: 0.0000899

Gnomad4 NFE exome AF: 0.000375

Gnomad4 OTH exome AF: 0.000221

GnomAD4 genome AF: 0.00000686 AC: 1 AN: 145810 Hom.: 0 Cov.: 0 AF XY: 0.0000141 AC XY: 1 AN XY: 70698

Gnomad4 AFR AF: 0.0000252

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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;