rs60936969

Positions:

• chr13-97985677-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002271.6(IPO5):​c.364+64T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,063,980 control chromosomes in the GnomAD database, including 107,490 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (10375 hom., cov: 30)
  • Exomes 𝑓: 0.45 (97115 hom.)
• Consequence: IPO5 NM_002271.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IPO5	NM_002271.6	c.364+64T>A		intron_variant		ENST00000651721.2	NP_002262.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IPO5	ENST00000651721.2	c.364+64T>A		intron_variant			NM_002271.6	ENSP00000499125	P1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 49306 AN: 147994 Hom.: 10376 Cov.: 30

Gnomad AFR AF: 0.0902

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.0232

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.315

GnomAD4 exome AF: 0.448 AC: 410181 AN: 915876 Hom.: 97115 AF XY: 0.448 AC XY: 212222 AN XY: 474206

Gnomad4 AFR exome AF: 0.0852

Gnomad4 AMR exome AF: 0.280

Gnomad4 ASJ exome AF: 0.390

Gnomad4 EAS exome AF: 0.0154

Gnomad4 SAS exome AF: 0.370

Gnomad4 FIN exome AF: 0.478

Gnomad4 NFE exome AF: 0.501

Gnomad4 OTH exome AF: 0.411

GnomAD4 genome AF: 0.333 AC: 49295 AN: 148104 Hom.: 10375 Cov.: 30 AF XY: 0.330 AC XY: 23868 AN XY: 72262

Gnomad4 AFR AF: 0.0901

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.0228

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.313

Alfa AF: 0.396 Hom.: 1659

Bravo AF: 0.302

Asia WGS AF: 0.167 AC: 579 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs60936969; hg19: chr13-98637931;