chr13-98014295-T-C

Position:

• chr13-98014295-T-C

Variant summary

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

The NM_002271.6(IPO5):​c.2325+81T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 1,038,698 control chromosomes in the GnomAD database, including 144,321 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 0.55 (24386 hom., cov: 31)
  • Exomes 𝑓: 0.51 (119935 hom.)
• Consequence: IPO5 NM_002271.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IPO5	NM_002271.6	c.2325+81T>C		intron_variant		ENST00000651721.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IPO5	ENST00000651721.2	c.2325+81T>C		intron_variant			NM_002271.6	P1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84192 AN: 151822 Hom.: 24352 Cov.: 31

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.442

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.507

GnomAD4 exome AF: 0.511 AC: 453273 AN: 886758 Hom.: 119935 AF XY: 0.511 AC XY: 230728 AN XY: 451402

Gnomad4 AFR exome AF: 0.748

Gnomad4 AMR exome AF: 0.363

Gnomad4 ASJ exome AF: 0.499

Gnomad4 EAS exome AF: 0.318

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.491

Gnomad4 NFE exome AF: 0.523

Gnomad4 OTH exome AF: 0.509

GnomAD4 genome AF: 0.555 AC: 84271 AN: 151940 Hom.: 24386 Cov.: 31 AF XY: 0.549 AC XY: 40766 AN XY: 74256

Gnomad4 AFR AF: 0.735

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.504

Alfa AF: 0.383 Hom.: 951

Bravo AF: 0.553

Asia WGS AF: 0.417 AC: 1452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.49
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6491395; hg19: chr13-98666549;