rs626716

chr13-97992999-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_002271.6(IPO5):c.777A>G(p.Leu259=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0574 in 1,613,432 control chromosomes in the GnomAD database, including 4,914 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 0.075 (694 hom., cov: 33)
  • Exomes 𝑓: 0.056 (4220 hom.)
• Consequence: IPO5 NM_002271.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=0.275 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IPO5	NM_002271.6	c.777A>G	p.Leu259=	synonymous_variant	10/29	ENST00000651721.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IPO5	ENST00000651721.2	c.777A>G	p.Leu259=	synonymous_variant	10/29		NM_002271.6	P1

Frequencies

GnomAD3 genomes AF: 0.0750 AC: 11414 AN: 152112 Hom.: 693 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0465

Gnomad ASJ AF: 0.0631

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.0415

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.0395

Gnomad OTH AF: 0.0684

GnomAD3 exomes AF: 0.0790 AC: 19842 AN: 251272 Hom.: 1636 AF XY: 0.0803 AC XY: 10908 AN XY: 135790

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.0280

Gnomad ASJ exome AF: 0.0632

Gnomad EAS exome AF: 0.331

Gnomad SAS exome AF: 0.140

Gnomad FIN exome AF: 0.0407

Gnomad NFE exome AF: 0.0420

Gnomad OTH exome AF: 0.0665

GnomAD4 exome AF: 0.0556 AC: 81254 AN: 1461202 Hom.: 4220 Cov.: 32 AF XY: 0.0580 AC XY: 42129 AN XY: 726812

Gnomad4 AFR exome AF: 0.113

Gnomad4 AMR exome AF: 0.0309

Gnomad4 ASJ exome AF: 0.0625

Gnomad4 EAS exome AF: 0.287

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.0432

Gnomad4 NFE exome AF: 0.0397

Gnomad4 OTH exome AF: 0.0725

GnomAD4 genome AF: 0.0751 AC: 11427 AN: 152230 Hom.: 694 Cov.: 33 AF XY: 0.0772 AC XY: 5744 AN XY: 74436

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0465

Gnomad4 ASJ AF: 0.0631

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.0415

Gnomad4 NFE AF: 0.0394

Gnomad4 OTH AF: 0.0715

Alfa AF: 0.0508 Hom.: 603

Bravo AF: 0.0774

Asia WGS AF: 0.232 AC: 804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	6.4
Dann	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs626716; hg19: chr13-98645253; COSMIC: COSV55154921; COSMIC: COSV55154921;