rs56411106

chr13-97993326-G-Achr13-97993326-G-T

Variant summary

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

The NM_002271.6(IPO5):c.913+101G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 952,710 control chromosomes in the GnomAD database, including 89,805 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 0.36 (11301 hom., cov: 33)
  • Exomes 𝑓: 0.42 (78504 hom.)
• Consequence: IPO5 NM_002271.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IPO5	NM_002271.6	c.913+101G>A		intron_variant		ENST00000651721.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IPO5	ENST00000651721.2	c.913+101G>A		intron_variant			NM_002271.6	P1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 55019 AN: 151974 Hom.: 11298 Cov.: 33

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.0227

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.338

GnomAD4 exome AF: 0.425 AC: 340054 AN: 800618 Hom.: 78504 AF XY: 0.425 AC XY: 175425 AN XY: 413062

Gnomad4 AFR exome AF: 0.192

Gnomad4 AMR exome AF: 0.275

Gnomad4 ASJ exome AF: 0.373

Gnomad4 EAS exome AF: 0.0149

Gnomad4 SAS exome AF: 0.350

Gnomad4 FIN exome AF: 0.472

Gnomad4 NFE exome AF: 0.476

Gnomad4 OTH exome AF: 0.402

GnomAD4 genome AF: 0.362 AC: 55023 AN: 152092 Hom.: 11301 Cov.: 33 AF XY: 0.358 AC XY: 26643 AN XY: 74340

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.0224

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.335

Alfa AF: 0.439 Hom.: 3113

Bravo AF: 0.342

Asia WGS AF: 0.178 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.7
Dann	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs56411106; hg19: chr13-98645580;