13-98006356-ATTTTTTTTTTTTTTTTTTTTTTTT-ATTTTTTTTTTTTTTTTTTTTTTTTTTTT

Variant names:

• chr13-98006356-A-ATTTT
• rs568589408
• NM_002271.6:c.1716+41_1716+44dupTTTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002271.6(IPO5):​c.1716+41_1716+44dupTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0036 (57 hom., cov: 0)
  • Exomes 𝑓: 0.0013 (5 hom.)
  • Failed GnomAD Quality Control
• Consequence: IPO5 NM_002271.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 57 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO5	NM_002271.6	c.1716+41_1716+44dupTTTT		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+8_1716+9insTTTT		intron_variant	Intron 17 of 28		NM_002271.6	ENSP00000499125.1

Frequencies

GnomAD3 genomes AF: 0.00356 AC: 224 AN: 62852 Hom.: 57 Cov.: 0

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00112

Gnomad ASJ AF: 0.00233

Gnomad EAS AF: 0.00162

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00215

Gnomad OTH AF: 0.00244

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00133 AC: 659 AN: 493808 Hom.: 5 Cov.: 0 AF XY: 0.00139 AC XY: 362 AN XY: 261108

Gnomad4 AFR exome AF: 0.00157

Gnomad4 AMR exome AF: 0.00119

Gnomad4 ASJ exome AF: 0.00155

Gnomad4 EAS exome AF: 0.000425

Gnomad4 SAS exome AF: 0.00252

Gnomad4 FIN exome AF: 0.00121

Gnomad4 NFE exome AF: 0.00120

Gnomad4 OTH exome AF: 0.00188

GnomAD4 genome AF: 0.00356 AC: 224 AN: 62862 Hom.: 57 Cov.: 0 AF XY: 0.00348 AC XY: 98 AN XY: 28162

Gnomad4 AFR AF: 0.0110

Gnomad4 AMR AF: 0.00112

Gnomad4 ASJ AF: 0.00233

Gnomad4 EAS AF: 0.00163

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00215

Gnomad4 OTH AF: 0.00241

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;