13-97990441-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_002271.6(IPO5):c.573G>A(p.Thr191=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000961 in 1,596,650 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00091 (23 hom.)
• Consequence: IPO5 NM_002271.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.719

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 13-97990441-G-A is Benign according to our data. Variant chr13-97990441-G-A is described in ClinVar as [Benign]. Clinvar id is 771466.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.719 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000906 (1308/1444344) while in subpopulation EAS AF= 0.0177 (701/39556). AF 95% confidence interval is 0.0166. There are 23 homozygotes in gnomad4_exome. There are 591 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IPO5	NM_002271.6	c.573G>A	p.Thr191=	synonymous_variant	9/29	ENST00000651721.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IPO5	ENST00000651721.2	c.573G>A	p.Thr191=	synonymous_variant	9/29		NM_002271.6	P1

Frequencies

GnomAD3 genomes AF: 0.00148 AC: 225 AN: 152188 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00870

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.0146

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00265 AC: 629 AN: 237778 Hom.: 10 AF XY: 0.00208 AC XY: 267 AN XY: 128402

Gnomad AFR exome AF: 0.000249

Gnomad AMR exome AF: 0.0116

Gnomad ASJ exome AF: 0.000521

Gnomad EAS exome AF: 0.0142

Gnomad SAS exome AF: 0.000338

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000544

Gnomad OTH exome AF: 0.000170

GnomAD4 exome AF: 0.000906 AC: 1308 AN: 1444344 Hom.: 23 Cov.: 29 AF XY: 0.000823 AC XY: 591 AN XY: 718210

Gnomad4 AFR exome AF: 0.000154

Gnomad4 AMR exome AF: 0.0117

Gnomad4 ASJ exome AF: 0.000389

Gnomad4 EAS exome AF: 0.0177

Gnomad4 SAS exome AF: 0.000621

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000217

Gnomad4 OTH exome AF: 0.000735

GnomAD4 genome AF: 0.00148 AC: 226 AN: 152306 Hom.: 2 Cov.: 33 AF XY: 0.00166 AC XY: 124 AN XY: 74482

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.00869

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.0148

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000244 Hom.: 0

Bravo AF: 0.00188

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Sep 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	6.4
Dann	Benign	0.82
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: rs145817156; hg19: chr13-98642695;