chr13-97985663-C-CT

Variant names:

• chr13-97985663-C-CT
• rs11366582
• NM_002271.6:c.364+64dupT

Variant summary

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

The NM_002271.6(IPO5):​c.364+64dupT 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 0.0022 (2 hom., cov: 0)
  • Exomes 𝑓: 0.031 (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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 2 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.364+64dupT		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+51insT		intron	N/A	ENSP00000499125.1	O00410-1
	IPO5	ENST00000261574.10	TSL:1	c.418+50_418+51insT		intron	N/A	ENSP00000261574.5	O00410-3
	IPO5	ENST00000490680.5	TSL:1	c.364+50_364+51insT		intron	N/A	ENSP00000418393.1	O00410-1

Frequencies

GnomAD3 genomes AF: 0.00223 AC: 325 AN: 145810 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00621

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00138

Gnomad ASJ AF: 0.000296

Gnomad EAS AF: 0.00102

Gnomad SAS AF: 0.00109

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000407

Gnomad OTH AF: 0.00348

GnomAD2 exomes AF: 0.0232 AC: 3019 AN: 130350 AF XY: 0.0219

Gnomad AFR exome AF: 0.0149

Gnomad AMR exome AF: 0.0406

Gnomad ASJ exome AF: 0.0221

Gnomad EAS exome AF: 0.0680

Gnomad FIN exome AF: 0.0137

Gnomad NFE exome AF: 0.0146

Gnomad OTH exome AF: 0.0296

GnomAD4 exome AF: 0.0310 AC: 24060 AN: 775806 Hom.: 0 Cov.: 0 AF XY: 0.0308 AC XY: 12413 AN XY: 403396

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

African (AFR) AF: 0.0215 AC: 362 AN: 16810

American (AMR) AF: 0.0417 AC: 1196 AN: 28710

Ashkenazi Jewish (ASJ) AF: 0.0359 AC: 658 AN: 18348

East Asian (EAS) AF: 0.0638 AC: 2057 AN: 32242

South Asian (SAS) AF: 0.0358 AC: 2056 AN: 57510

European-Finnish (FIN) AF: 0.0228 AC: 998 AN: 43866

Middle Eastern (MID) AF: 0.0274 AC: 90 AN: 3290

European-Non Finnish (NFE) AF: 0.0288 AC: 15521 AN: 539210

Other (OTH) AF: 0.0313 AC: 1122 AN: 35820

⚠️ 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: 0.00222 AC: 324 AN: 145864 Hom.: 2 Cov.: 0 AF XY: 0.00232 AC XY: 164 AN XY: 70764

African (AFR) AF: 0.00617 AC: 245 AN: 39734

American (AMR) AF: 0.00138 AC: 20 AN: 14514

Ashkenazi Jewish (ASJ) AF: 0.000296 AC: 1 AN: 3382

East Asian (EAS) AF: 0.00103 AC: 5 AN: 4876

South Asian (SAS) AF: 0.00110 AC: 5 AN: 4558

European-Finnish (FIN) AF: 0.00151 AC: 14 AN: 9300

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

European-Non Finnish (NFE) AF: 0.000407 AC: 27 AN: 66322

Other (OTH) AF: 0.00346 AC: 7 AN: 2026

Alfa AF: 0.00 Hom.: 584

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.8
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: rs11366582; hg19: chr13-98637917;