13-98006356-ATTTTTTTTTTTTTTTTTTTTTTTT-ATTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

Variant names:

• chr13-98006356-A-ATTTTTTTTT
• rs568589408
• NM_002271.6:c.1716+36_1716+44dupTTTTTTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_002271.6(IPO5):​c.1716+36_1716+44dupTTTTTTTTT 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 0.0043 (74 hom., cov: 0)
  • Exomes 𝑓: 0.00018 (3 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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00431 (271/62858) while in subpopulation AFR AF= 0.0201 (233/11606). AF 95% confidence interval is 0.018. There are 74 homozygotes in gnomad4. There are 127 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 74 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO5	NM_002271.6	c.1716+36_1716+44dupTTTTTTTTT		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+9insTTTTTTTTT		intron_variant	Intron 17 of 28		NM_002271.6	ENSP00000499125.1

Frequencies

GnomAD3 genomes AF: 0.00431 AC: 271 AN: 62848 Hom.: 74 Cov.: 0

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00134

Gnomad ASJ AF: 0.000931

Gnomad EAS AF: 0.00243

Gnomad SAS AF: 0.00159

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000512

Gnomad OTH AF: 0.00244

GnomAD4 exome AF: 0.000182 AC: 90 AN: 493928 Hom.: 3 Cov.: 0 AF XY: 0.000226 AC XY: 59 AN XY: 261174

Gnomad4 AFR exome AF: 0.000525

Gnomad4 AMR exome AF: 0.000170

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000533

Gnomad4 SAS exome AF: 0.000959

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000705

Gnomad4 OTH exome AF: 0.000188

GnomAD4 genome AF: 0.00431 AC: 271 AN: 62858 Hom.: 74 Cov.: 0 AF XY: 0.00451 AC XY: 127 AN XY: 28158

Gnomad4 AFR AF: 0.0201

Gnomad4 AMR AF: 0.00134

Gnomad4 ASJ AF: 0.000931

Gnomad4 EAS AF: 0.00245

Gnomad4 SAS AF: 0.00159

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000512

Gnomad4 OTH AF: 0.00242

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;