Variant 5-62476703-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_016338.5(IPO11):c.778A>G(p.Asn260Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00729 in 1,519,188 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0064 ( 8 hom., cov: 33)

Exomes 𝑓: 0.0074 ( 45 hom. )

Consequence

IPO11
NM_016338.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.33

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038756132).

BP6

Variant 5-62476703-A-G is Benign according to our data. Variant chr5-62476703-A-G is described in ClinVar as [Benign]. Clinvar id is 781996.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IPO11	NM_016338.5 linkuse as main transcript	c.778A>G	p.Asn260Asp	missense_variant	9/30	ENST00000325324.11
IPO11	NM_001134779.2 linkuse as main transcript	c.898A>G	p.Asn300Asp	missense_variant	9/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IPO11	ENST00000325324.11 linkuse as main transcript	c.778A>G	p.Asn260Asp	missense_variant	9/30	1	NM_016338.5	P1	Q9UI26-1
IPO11	ENST00000409296.7 linkuse as main transcript	c.898A>G	p.Asn300Asp	missense_variant	9/30	2			Q9UI26-2
IPO11	ENST00000424533.5 linkuse as main transcript	c.778A>G	p.Asn260Asp	missense_variant, NMD_transcript_variant	9/29	2
IPO11	ENST00000507640.1 linkuse as main transcript	n.168+2239A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00643

AC:

979

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.00491

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00527

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0100

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00630

AC:

1250

AN:

198306

Hom.:

AF XY:

0.00630

AC XY:

685

AN XY:

108654

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00225

Gnomad ASJ exome

AF:

0.0137

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000961

Gnomad FIN exome

AF:

0.00756

Gnomad NFE exome

AF:

0.00876

Gnomad OTH exome

AF:

0.00737

GnomAD4 exome

AF:

0.00738

AC:

10090

AN:

1366864

Hom.:

Cov.:

AF XY:

0.00737

AC XY:

4993

AN XY:

677794

show subpopulations

Gnomad4 AFR exome

AF:

0.00106

Gnomad4 AMR exome

AF:

0.00245

Gnomad4 ASJ exome

AF:

0.0112

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00107

Gnomad4 FIN exome

AF:

0.00638

Gnomad4 NFE exome

AF:

0.00841

Gnomad4 OTH exome

AF:

0.00647

GnomAD4 genome

AF:

0.00643

AC:

979

AN:

152324

Hom.:

Cov.:

AF XY:

0.00610

AC XY:

454

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00490

Gnomad4 ASJ

AF:

0.0107

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00527

Gnomad4 NFE

AF:

0.0100

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00930

Hom.:

Bravo

AF:

0.00635

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.00160

AC:

ESP6500EA

AF:

0.0102

AC:

ExAC

AF:

0.00618

AC:

750

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.43

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.016

T;.

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.85

T;T

MetaRNN

Benign

0.0039

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;.

MutationTaster

Benign

0.94

D;D

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.77

N;N

REVEL

Benign

0.050

Sift

Benign

0.61

T;T

Sift4G

Benign

0.66

T;T

Polyphen

0.0010

B;B

Vest4

0.38

MVP

0.50

MPC

0.22

ClinPred

0.011

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.088

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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