13-98006356-ATTTTTTTTTTTTTTTTTTTTTTTT-ATTTTTTTTTTTTTTTTTTTTTTT

Variant names:

• chr13-98006356-AT-A
• rs568589408
• NM_002271.6:c.1716+44delT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002271.6(IPO5):​c.1716+44delT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0049 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IPO5 NM_002271.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• 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: Uncertain_significance. The variant received 0 ACMG points.

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

Frequencies

GnomAD3 genomes AF: 0.00126 AC: 79 AN: 62840 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00492

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00135

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000406

Gnomad SAS AF: 0.00159

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000296

Gnomad OTH AF: 0.00122

GnomAD4 exome AF: 0.00489 AC: 2409 AN: 492158 Hom.: 0 Cov.: 0 AF XY: 0.00496 AC XY: 1291 AN XY: 260238

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

African (AFR) AF: 0.00316 AC: 18 AN: 5698

American (AMR) AF: 0.00564 AC: 99 AN: 17544

Ashkenazi Jewish (ASJ) AF: 0.00632 AC: 69 AN: 10920

East Asian (EAS) AF: 0.00186 AC: 35 AN: 18798

South Asian (SAS) AF: 0.00840 AC: 400 AN: 47606

European-Finnish (FIN) AF: 0.00592 AC: 166 AN: 28060

Middle Eastern (MID) AF: 0.00456 AC: 13 AN: 2852

European-Non Finnish (NFE) AF: 0.00442 AC: 1500 AN: 339474

Other (OTH) AF: 0.00514 AC: 109 AN: 21206

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00126 AC: 79 AN: 62850 Hom.: 1 Cov.: 0 AF XY: 0.00114 AC XY: 32 AN XY: 28158

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

African (AFR) AF: 0.00491 AC: 57 AN: 11602

American (AMR) AF: 0.00134 AC: 6 AN: 4470

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

East Asian (EAS) AF: 0.000409 AC: 1 AN: 2446

South Asian (SAS) AF: 0.00159 AC: 3 AN: 1886

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1706

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

European-Non Finnish (NFE) AF: 0.000296 AC: 11 AN: 37130

Other (OTH) AF: 0.00120 AC: 1 AN: 830

⚠️ 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.: 53

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.0050

Splicing

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

Other links and lift over

dbSNP: rs568589408; hg19: chr13-98658610;