Variant 5-62476706-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016338.5(IPO11):c.781G>A(p.Val261Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000559 in 1,521,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

IPO11
NM_016338.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.122

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17890513).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IPO11	NM_016338.5 linkuse as main transcript	c.781G>A	p.Val261Met	missense_variant	9/30	ENST00000325324.11
IPO11	NM_001134779.2 linkuse as main transcript	c.901G>A	p.Val301Met	missense_variant	9/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IPO11	ENST00000325324.11 linkuse as main transcript	c.781G>A	p.Val261Met	missense_variant	9/30	1	NM_016338.5	P1	Q9UI26-1
IPO11	ENST00000409296.7 linkuse as main transcript	c.901G>A	p.Val301Met	missense_variant	9/30	2			Q9UI26-2
IPO11	ENST00000424533.5 linkuse as main transcript	c.781G>A	p.Val261Met	missense_variant, NMD_transcript_variant	9/29	2
IPO11	ENST00000507640.1 linkuse as main transcript	n.168+2242G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000251

AC:

AN:

199114

Hom.:

AF XY:

0.0000275

AC XY:

AN XY:

109096

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000513

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000569

AC:

AN:

1369678

Hom.:

Cov.:

AF XY:

0.0000530

AC XY:

AN XY:

679186

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000704

Gnomad4 OTH exome

AF:

0.0000354

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000580

Hom.:

Bravo

AF:

0.0000378

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

Jun 27, 2022

The c.901G>A (p.V301M) 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 901, causing the valine (V) at amino acid position 301 to be replaced by a methionine (M). 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

0.086

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.42

Cadd

Benign

Dann

Uncertain

0.97

DEOGEN2

Benign

0.026

T;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.49

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.047

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.0

L;.

MutationTaster

Benign

0.80

D;D

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.26

N;N

REVEL

Benign

0.041

Sift

Benign

0.088

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.24

B;P

Vest4

0.35

MVP

0.32

MPC

0.25

ClinPred

0.069

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.029

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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