13-98006356-A-ATTTTT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_002271.6(IPO5):c.1716+40_1716+44dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (42 hom., cov: 0)
  • Exomes 𝑓: 0.00052 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: IPO5 NM_002271.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00500

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 13-98006356-A-ATTTTT is Benign according to our data. Variant chr13-98006356-A-ATTTTT is described in ClinVar as [Likely_benign]. Clinvar id is 2643882.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 42 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IPO5	NM_002271.6	c.1716+40_1716+44dup		intron_variant		ENST00000651721.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IPO5	ENST00000651721.2	c.1716+40_1716+44dup		intron_variant			NM_002271.6	P1

Frequencies

GnomAD3 genomes AF: 0.00210 AC: 132 AN: 62844 Hom.: 42 Cov.: 0

Gnomad AFR AF: 0.00950

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000529

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000539

Gnomad OTH AF: 0.00122

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000516 AC: 255 AN: 493922 Hom.: 3 Cov.: 0 AF XY: 0.000513 AC XY: 134 AN XY: 261160

Gnomad4 AFR exome AF: 0.000701

Gnomad4 AMR exome AF: 0.000170

Gnomad4 ASJ exome AF: 0.000456

Gnomad4 EAS exome AF: 0.000159

Gnomad4 SAS exome AF: 0.00131

Gnomad4 FIN exome AF: 0.000426

Gnomad4 NFE exome AF: 0.000429

Gnomad4 OTH exome AF: 0.000845

GnomAD4 genome AF: 0.00210 AC: 132 AN: 62854 Hom.: 42 Cov.: 0 AF XY: 0.00227 AC XY: 64 AN XY: 28154

Gnomad4 AFR AF: 0.00948

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000530

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000539

Gnomad4 OTH AF: 0.00120

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

IPO5: BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs568589408; hg19: chr13-98658610;