rs17190392

Positions:

• chr13-98023697-A-G

Variant summary

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

The NM_002271.6(IPO5):​c.*1875A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 152,034 control chromosomes in the GnomAD database, including 11,382 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 (11382 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IPO5 NM_002271.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.894

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IPO5	NM_002271.6	c.*1875A>G		3_prime_UTR_variant	29/29	ENST00000651721.2	NP_002262.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IPO5	ENST00000651721.2	c.*1875A>G		3_prime_UTR_variant	29/29		NM_002271.6	ENSP00000499125.1
IPO5	ENST00000261574.10	c.*1875A>G		3_prime_UTR_variant	29/29	1		ENSP00000261574.5

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55264 AN: 151916 Hom.: 11380 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.0227

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.340

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.364 AC: 55266 AN: 152034 Hom.: 11382 Cov.: 32 AF XY: 0.360 AC XY: 26779 AN XY: 74298

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.0224

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.336

Alfa AF: 0.438 Hom.: 16408

Bravo AF: 0.344

Asia WGS AF: 0.179 AC: 621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.52
DANN	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17190392; hg19: chr13-98675951;