13-98006356-ATTTTTTTTTTTTTTTTTTTTTTTT-ATTTTTTTTTT

Variant names:

• chr13-98006356-ATTTTTTTTTTTTTT-A
• rs568589408
• NM_002271.6:c.1716+31_1716+44delTTTTTTTTTTTTTT

Variant summary

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

The NM_002271.6(IPO5):​c.1716+31_1716+44delTTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00487 in 492,422 control chromosomes in the GnomAD database, including 25 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0041 (2 hom., cov: 0)
  • Exomes 𝑓: 0.0049 (25 hom.)
  • Failed GnomAD Quality Control
• Consequence: IPO5 NM_002271.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

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_exome allele frequency = 0.00487 (2398/492422) while in subpopulation AFR AF= 0.0244 (139/5696). AF 95% confidence interval is 0.0211. There are 25 homozygotes in gnomad4_exome. There are 1271 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 25 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO5	NM_002271.6	c.1716+31_1716+44delTTTTTTTTTTTTTT		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+9_1716+22delTTTTTTTTTTTTTT		intron_variant	Intron 17 of 28		NM_002271.6	ENSP00000499125.1

Frequencies

GnomAD3 genomes AF: 0.00412 AC: 259 AN: 62842 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.0169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00605

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000406

Gnomad SAS AF: 0.000529

Gnomad FIN AF: 0.000586

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000808

Gnomad OTH AF: 0.00488

GnomAD4 exome AF: 0.00487 AC: 2398 AN: 492422 Hom.: 25 AF XY: 0.00488 AC XY: 1271 AN XY: 260330

Gnomad4 AFR exome AF: 0.0244

Gnomad4 AMR exome AF: 0.0142

Gnomad4 ASJ exome AF: 0.00641

Gnomad4 EAS exome AF: 0.0105

Gnomad4 SAS exome AF: 0.00418

Gnomad4 FIN exome AF: 0.00331

Gnomad4 NFE exome AF: 0.00381

Gnomad4 OTH exome AF: 0.00697

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00414 AC: 260 AN: 62852 Hom.: 2 Cov.: 0 AF XY: 0.00437 AC XY: 123 AN XY: 28158

Gnomad4 AFR AF: 0.0168

Gnomad4 AMR AF: 0.00603

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000408

Gnomad4 SAS AF: 0.000530

Gnomad4 FIN AF: 0.000586

Gnomad4 NFE AF: 0.000808

Gnomad4 OTH AF: 0.00602

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;