13-97985663-CTTTTT-CTTT

Variant names:

• chr13-97985663-CTT-C
• rs11366582
• NM_002271.6:c.364+63_364+64delTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_002271.6(IPO5):​c.364+63_364+64delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0322 in 896,014 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00070 (0 hom., cov: 0)
  • Exomes 𝑓: 0.038 (2 hom.)
• Consequence: IPO5 NM_002271.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO5	NM_002271.6	c.364+63_364+64delTT		intron_variant	Intron 6 of 28	ENST00000651721.2	NP_002262.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPO5	ENST00000651721.2	c.364+51_364+52delTT		intron_variant	Intron 6 of 28		NM_002271.6	ENSP00000499125.1

Frequencies

GnomAD3 genomes AF: 0.000700 AC: 102 AN: 145624 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000345

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000655

Gnomad FIN AF: 0.00227

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000377

Gnomad OTH AF: 0.000498

GnomAD2 exomes AF: 0.0411 AC: 5359 AN: 130350 AF XY: 0.0422

Gnomad AFR exome AF: 0.0733

Gnomad AMR exome AF: 0.0340

Gnomad ASJ exome AF: 0.0472

Gnomad EAS exome AF: 0.0195

Gnomad FIN exome AF: 0.0298

Gnomad NFE exome AF: 0.0410

Gnomad OTH exome AF: 0.0382

GnomAD4 exome AF: 0.0384 AC: 28776 AN: 750336 Hom.: 2 AF XY: 0.0387 AC XY: 15085 AN XY: 389844

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0882 AC: 1418 AN: 16070

American (AMR) AF: 0.0285 AC: 802 AN: 28122

Ashkenazi Jewish (ASJ) AF: 0.0359 AC: 639 AN: 17812

East Asian (EAS) AF: 0.0170 AC: 557 AN: 32720

South Asian (SAS) AF: 0.0420 AC: 2346 AN: 55888

European-Finnish (FIN) AF: 0.0312 AC: 1315 AN: 42208

Middle Eastern (MID) AF: 0.0288 AC: 93 AN: 3224

European-Non Finnish (NFE) AF: 0.0390 AC: 20284 AN: 519752

Other (OTH) AF: 0.0383 AC: 1322 AN: 34540

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000700 AC: 102 AN: 145678 Hom.: 0 Cov.: 0 AF XY: 0.000722 AC XY: 51 AN XY: 70644

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00118 AC: 47 AN: 39722

American (AMR) AF: 0.000345 AC: 5 AN: 14496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3380

East Asian (EAS) AF: 0.00 AC: 0 AN: 4876

South Asian (SAS) AF: 0.000658 AC: 3 AN: 4558

European-Finnish (FIN) AF: 0.00227 AC: 21 AN: 9242

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.000377 AC: 25 AN: 66230

Other (OTH) AF: 0.000495 AC: 1 AN: 2022

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 584

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.098
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11366582; hg19: chr13-98637917;