13-98006356-ATTTTTTTTTTTTTTTTTTTTTTTT-ATTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

Variant names:

• chr13-98006356-A-ATTTTTTTTTTT
• rs568589408
• NM_002271.6:c.1716+34_1716+44dupTTTTTTTTTTT

Variant summary

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

The NM_002271.6(IPO5):​c.1716+34_1716+44dupTTTTTTTTTTT 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 0.0019 (21 hom., cov: 0)
  • Exomes 𝑓: 0.000097 (0 hom.)
• 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 21 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO5	NM_002271.6	c.1716+34_1716+44dupTTTTTTTTTTT		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+9insTTTTTTTTTTT		intron_variant	Intron 17 of 28		NM_002271.6	ENSP00000499125.1

Frequencies

GnomAD3 genomes AF: 0.00193 AC: 121 AN: 62852 Hom.: 21 Cov.: 0

Gnomad AFR AF: 0.00604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000224

Gnomad ASJ AF: 0.00140

Gnomad EAS AF: 0.00894

Gnomad SAS AF: 0.00106

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000592

Gnomad OTH AF: 0.00122

GnomAD4 exome AF: 0.0000972 AC: 48 AN: 493970 Hom.: 0 Cov.: 0 AF XY: 0.000115 AC XY: 30 AN XY: 261190

Gnomad4 AFR exome AF: 0.000350

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000905

Gnomad4 SAS exome AF: 0.000500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000881

Gnomad4 OTH exome AF: 0.0000938

GnomAD4 genome AF: 0.00192 AC: 121 AN: 62862 Hom.: 21 Cov.: 0 AF XY: 0.00170 AC XY: 48 AN XY: 28160

Gnomad4 AFR AF: 0.00603

Gnomad4 AMR AF: 0.000224

Gnomad4 ASJ AF: 0.00140

Gnomad4 EAS AF: 0.00900

Gnomad4 SAS AF: 0.00106

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000592

Gnomad4 OTH AF: 0.00120

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;