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. The variant received -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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• 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: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002271.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPO5	NM_002271.6	MANE Select	c.1716+28_1716+44delTTTTTTTTTTTTTTTTT		intron	N/A	NP_002262.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPO5	ENST00000651721.2	MANE Select	c.1716+9_1716+25delTTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000499125.1	O00410-1
	IPO5	ENST00000261574.10	TSL:1	c.1770+9_1770+25delTTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000261574.5	O00410-3
	IPO5	ENST00000490680.5	TSL:1	c.1716+9_1716+25delTTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000418393.1	O00410-1

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

African (AFR) AF: 0.00612 AC: 35 AN: 5716

American (AMR) AF: 0.00637 AC: 112 AN: 17592

Ashkenazi Jewish (ASJ) AF: 0.0145 AC: 159 AN: 10936

East Asian (EAS) AF: 0.0841 AC: 1562 AN: 18572

South Asian (SAS) AF: 0.0192 AC: 917 AN: 47708

European-Finnish (FIN) AF: 0.00654 AC: 184 AN: 28146

Middle Eastern (MID) AF: 0.0105 AC: 30 AN: 2848

European-Non Finnish (NFE) AF: 0.00901 AC: 3065 AN: 340312

Other (OTH) AF: 0.0159 AC: 339 AN: 21282

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

African (AFR) AF: 0.00155 AC: 18 AN: 11606

American (AMR) AF: 0.000671 AC: 3 AN: 4474

Ashkenazi Jewish (ASJ) AF: 0.000466 AC: 1 AN: 2148

East Asian (EAS) AF: 0.000817 AC: 2 AN: 2448

South Asian (SAS) AF: 0.00 AC: 0 AN: 1886

European-Finnish (FIN) AF: 0.00176 AC: 3 AN: 1706

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 88

European-Non Finnish (NFE) AF: 0.000512 AC: 19 AN: 37132

Other (OTH) AF: 0.00 AC: 0 AN: 830

Alfa AF: 0.00 Hom.: 53

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs568589408;

hg19: chr13-98658610;