13-97985663-C-CTTT

Variant names:

• chr13-97985663-C-CTTT
• rs11366582
• NM_002271.6:c.364+62_364+64dupTTT

Variant summary

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

The NM_002271.6(IPO5):​c.364+62_364+64dupTTT 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: not found (cov: 0)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: IPO5 NM_002271.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76
• 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.364+62_364+64dupTTT		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.364+50_364+51insTTT		intron	N/A	ENSP00000499125.1	O00410-1
	IPO5	ENST00000261574.10	TSL:1	c.418+50_418+51insTTT		intron	N/A	ENSP00000261574.5	O00410-3
	IPO5	ENST00000490680.5	TSL:1	c.364+50_364+51insTTT		intron	N/A	ENSP00000418393.1	O00410-1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000229 AC: 18 AN: 785902 Hom.: 0 Cov.: 0 AF XY: 0.0000220 AC XY: 9 AN XY: 408694

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

African (AFR) AF: 0.00 AC: 0 AN: 16950

American (AMR) AF: 0.00 AC: 0 AN: 29186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18688

East Asian (EAS) AF: 0.0000596 AC: 2 AN: 33574

South Asian (SAS) AF: 0.0000342 AC: 2 AN: 58410

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3338

European-Non Finnish (NFE) AF: 0.0000239 AC: 13 AN: 544856

Other (OTH) AF: 0.0000275 AC: 1 AN: 36336

⚠️ 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 Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.8

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: rs11366582; hg19: chr13-98637917;