Variant 5-62476686-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016338.5(IPO11):c.761G>A(p.Arg254Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000588 in 1,360,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000059 ( 0 hom. )

Consequence

IPO11
NM_016338.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.27

Variant links:

Genes affected

IPO11 (HGNC:20628): (importin 11) Importins, including IPO11, are a members of the karyopherin/importin-beta family of transport receptors (see KPNB1; 602738) that mediate nucleocytoplasmic transport of protein and RNA cargoes (Plafker and Macara, 2000 [PubMed 11032817]).[supplied by OMIM, Sep 2008]

IPO11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38907203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IPO11	NM_016338.5 linkuse as main transcript	c.761G>A	p.Arg254Lys	missense_variant	9/30	ENST00000325324.11
IPO11	NM_001134779.2 linkuse as main transcript	c.881G>A	p.Arg294Lys	missense_variant	9/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IPO11	ENST00000325324.11 linkuse as main transcript	c.761G>A	p.Arg254Lys	missense_variant	9/30	1	NM_016338.5	P1	Q9UI26-1
IPO11	ENST00000409296.7 linkuse as main transcript	c.881G>A	p.Arg294Lys	missense_variant	9/30	2			Q9UI26-2
IPO11	ENST00000424533.5 linkuse as main transcript	c.761G>A	p.Arg254Lys	missense_variant, NMD_transcript_variant	9/29	2
IPO11	ENST00000507640.1 linkuse as main transcript	n.168+2222G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000103

AC:

AN:

194124

Hom.:

AF XY:

0.00000940

AC XY:

AN XY:

106418

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000771

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000105

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000588

AC:

AN:

1360004

Hom.:

Cov.:

AF XY:

0.00000742

AC XY:

AN XY:

673854

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000285

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000566

Gnomad4 OTH exome

AF:

0.0000178

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 30, 2023

The c.881G>A (p.R294K) alteration is located in exon 9 (coding exon 9) of the IPO11 gene. This alteration results from a G to A substitution at nucleotide position 881, causing the arginine (R) at amino acid position 294 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.0098

T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

0.096

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.39

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.98

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

0.31

N;N

REVEL

Benign

0.22

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0040

B;B

Vest4

0.68

MutPred

0.47

Gain of ubiquitination at R254 (P = 0.0138);.;

MVP

0.80

MPC

0.20

ClinPred

0.24

GERP RS

5.5

Varity_R

0.28

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over