13-98006356-ATTTTTTTTTTTTTTTTTTTTTTTT-ATTTTTTT

Variant names:

• chr13-98006356-ATTTTTTTTTTTTTTTTT-A
• rs568589408
• NM_002271.6:c.1716+28_1716+44delTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002271.6(IPO5):​c.1716+28_1716+44delTTTTTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 555,974 control chromosomes in the GnomAD database, including 100 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00073 (1 hom., cov: 0)
  • Exomes 𝑓: 0.013 (99 hom.)
• 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.

• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO5	NM_002271.6	c.1716+28_1716+44delTTTTTTTTTTTTTTTTT		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+25delTTTTTTTTTTTTTTTTT		intron_variant	Intron 17 of 28		NM_002271.6	ENSP00000499125.1

Frequencies

GnomAD3 genomes AF: 0.000732 AC: 46 AN: 62852 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000672

Gnomad ASJ AF: 0.000466

Gnomad EAS AF: 0.000811

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00176

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000512

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0130 AC: 6403 AN: 493112 Hom.: 99 AF XY: 0.0131 AC XY: 3412 AN XY: 260678

Gnomad4 AFR exome AF: 0.00612

Gnomad4 AMR exome AF: 0.00637

Gnomad4 ASJ exome AF: 0.0145

Gnomad4 EAS exome AF: 0.0841

Gnomad4 SAS exome AF: 0.0192

Gnomad4 FIN exome AF: 0.00654

Gnomad4 NFE exome AF: 0.00901

Gnomad4 OTH exome AF: 0.0159

GnomAD4 genome AF: 0.000732 AC: 46 AN: 62862 Hom.: 1 Cov.: 0 AF XY: 0.000710 AC XY: 20 AN XY: 28162

Gnomad4 AFR AF: 0.00155

Gnomad4 AMR AF: 0.000671

Gnomad4 ASJ AF: 0.000466

Gnomad4 EAS AF: 0.000817

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00176

Gnomad4 NFE AF: 0.000512

Gnomad4 OTH AF: 0.00

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;