13-98006356-ATTTTTTTTTTTTTTTTTTTTTTTT-ATTTTTTTTT

Variant names:

• chr13-98006356-ATTTTTTTTTTTTTTT-A
• rs568589408
• NM_002271.6:c.1716+30_1716+44delTTTTTTTTTTTTTTT

Variant summary

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

The NM_002271.6(IPO5):​c.1716+30_1716+44delTTTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0085 in 555,936 control chromosomes in the GnomAD database, including 75 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0028 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0092 (74 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 = 0.052 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO5	NM_002271.6	c.1716+30_1716+44delTTTTTTTTTTTTTTT		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+23delTTTTTTTTTTTTTTT		intron_variant	Intron 17 of 28		NM_002271.6	ENSP00000499125.1

Frequencies

GnomAD3 genomes AF: 0.00278 AC: 175 AN: 62852 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00224

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00112

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0175

Gnomad SAS AF: 0.0206

Gnomad FIN AF: 0.0152

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000915

Gnomad OTH AF: 0.00244

GnomAD4 exome AF: 0.00922 AC: 4548 AN: 493074 Hom.: 74 AF XY: 0.00954 AC XY: 2488 AN XY: 260704

Gnomad4 AFR exome AF: 0.0104

Gnomad4 AMR exome AF: 0.00593

Gnomad4 ASJ exome AF: 0.00677

Gnomad4 EAS exome AF: 0.0548

Gnomad4 SAS exome AF: 0.0168

Gnomad4 FIN exome AF: 0.00970

Gnomad4 NFE exome AF: 0.00572

Gnomad4 OTH exome AF: 0.0116

GnomAD4 genome AF: 0.00280 AC: 176 AN: 62862 Hom.: 1 Cov.: 0 AF XY: 0.00334 AC XY: 94 AN XY: 28158

Gnomad4 AFR AF: 0.00224

Gnomad4 AMR AF: 0.00112

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0176

Gnomad4 SAS AF: 0.0207

Gnomad4 FIN AF: 0.0152

Gnomad4 NFE AF: 0.000916

Gnomad4 OTH AF: 0.00361

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;