13-98006356-ATTTTTTTTTTTTTTTTTTTTTTTT-ATTTTTTTTTTTTTTTTTTTTTTTTTT

Variant names:

• chr13-98006356-A-ATT
• rs568589408
• NM_002271.6:c.1716+43_1716+44dupTT

Variant summary

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

The NM_002271.6(IPO5):​c.1716+43_1716+44dupTT 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 0.020 (339 hom., cov: 0)
  • Exomes 𝑓: 0.0050 (19 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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0198 (1246/62848) while in subpopulation AFR AF= 0.0288 (334/11592). AF 95% confidence interval is 0.0263. There are 339 homozygotes in gnomad4. There are 563 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 339 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO5	NM_002271.6	c.1716+43_1716+44dupTT		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+9insTT		intron_variant	Intron 17 of 28		NM_002271.6	ENSP00000499125.1

Frequencies

GnomAD3 genomes AF: 0.0198 AC: 1247 AN: 62838 Hom.: 339 Cov.: 0

Gnomad AFR AF: 0.0289

Gnomad AMI AF: 0.0349

Gnomad AMR AF: 0.0184

Gnomad ASJ AF: 0.0158

Gnomad EAS AF: 0.0101

Gnomad SAS AF: 0.00952

Gnomad FIN AF: 0.00469

Gnomad MID AF: 0.0109

Gnomad NFE AF: 0.0191

Gnomad OTH AF: 0.0195

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00497 AC: 2452 AN: 492988 Hom.: 19 Cov.: 0 AF XY: 0.00513 AC XY: 1338 AN XY: 260648

Gnomad4 AFR exome AF: 0.00403

Gnomad4 AMR exome AF: 0.00466

Gnomad4 ASJ exome AF: 0.00476

Gnomad4 EAS exome AF: 0.00154

Gnomad4 SAS exome AF: 0.00929

Gnomad4 FIN exome AF: 0.00502

Gnomad4 NFE exome AF: 0.00459

Gnomad4 OTH exome AF: 0.00527

GnomAD4 genome AF: 0.0198 AC: 1246 AN: 62848 Hom.: 339 Cov.: 0 AF XY: 0.0200 AC XY: 563 AN XY: 28156

Gnomad4 AFR AF: 0.0288

Gnomad4 AMR AF: 0.0183

Gnomad4 ASJ AF: 0.0158

Gnomad4 EAS AF: 0.00980

Gnomad4 SAS AF: 0.00954

Gnomad4 FIN AF: 0.00469

Gnomad4 NFE AF: 0.0191

Gnomad4 OTH AF: 0.0193

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;