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. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

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. 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 0.0028 (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
• 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.

• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0028 (176/62862) while in subpopulation SAS AF = 0.0207 (39/1886). AF 95% confidence interval is 0.0155. There are 1 homozygotes in GnomAd4. There are 94 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 74 gene

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+30_1716+44delTTTTTTTTTTTTTTT		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+23delTTTTTTTTTTTTTTT		intron	N/A	ENSP00000499125.1	O00410-1
	IPO5	ENST00000261574.10	TSL:1	c.1770+9_1770+23delTTTTTTTTTTTTTTT		intron	N/A	ENSP00000261574.5	O00410-3
	IPO5	ENST00000490680.5	TSL:1	c.1716+9_1716+23delTTTTTTTTTTTTTTT		intron	N/A	ENSP00000418393.1	O00410-1

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

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

African (AFR) AF: 0.0104 AC: 59 AN: 5700

American (AMR) AF: 0.00593 AC: 104 AN: 17538

Ashkenazi Jewish (ASJ) AF: 0.00677 AC: 74 AN: 10936

East Asian (EAS) AF: 0.0548 AC: 1026 AN: 18712

South Asian (SAS) AF: 0.0168 AC: 803 AN: 47782

European-Finnish (FIN) AF: 0.00970 AC: 273 AN: 28132

Middle Eastern (MID) AF: 0.00596 AC: 17 AN: 2854

European-Non Finnish (NFE) AF: 0.00572 AC: 1946 AN: 340146

Other (OTH) AF: 0.0116 AC: 246 AN: 21274

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

African (AFR) AF: 0.00224 AC: 26 AN: 11608

American (AMR) AF: 0.00112 AC: 5 AN: 4474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2148

East Asian (EAS) AF: 0.0176 AC: 43 AN: 2446

South Asian (SAS) AF: 0.0207 AC: 39 AN: 1886

European-Finnish (FIN) AF: 0.0152 AC: 26 AN: 1706

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

European-Non Finnish (NFE) AF: 0.000916 AC: 34 AN: 37132

Other (OTH) AF: 0.00361 AC: 3 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;