Variant 5-62476689-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_016338.5(IPO11):c.764G>A(p.Ser255Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000732 in 1,366,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

IPO11
NM_016338.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0290

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:

ENSG00000288643 (HGNC:):

ENSG00000288643 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07969165).

BP6

Variant 5-62476689-G-A is Benign according to our data. Variant chr5-62476689-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3286302.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IPO11	NM_016338.5 linkuse as main transcript	c.764G>A	p.Ser255Asn	missense_variant	9/30	ENST00000325324.11	NP_057422.3	Q9UI26-1
IPO11	NM_001134779.2 linkuse as main transcript	c.884G>A	p.Ser295Asn	missense_variant	9/30		NP_001128251.1	Q9UI26-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IPO11	ENST00000325324.11 linkuse as main transcript	c.764G>A	p.Ser255Asn	missense_variant	9/30	1	NM_016338.5	ENSP00000316651.6	Q9UI26-1
IPO11	ENST00000424533.5 linkuse as main transcript	n.764G>A		non_coding_transcript_exon_variant	9/29	2		ENSP00000395685.1	F8WDV0
ENSG00000288643	ENST00000509663.2 linkuse as main transcript	n.65-38699G>A		intron_variant		3		ENSP00000502199.1	A0A6Q8PGD0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.32e-7

AC:

AN:

1366062

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

676992

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:

9.41e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 16, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.4

DANN

Benign

0.56

DEOGEN2

Benign

0.015

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.58

T;T

M_CAP

Benign

0.0091

MetaRNN

Benign

0.080

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.14

N;.

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.090

Sift

Benign

0.65

T;T

Sift4G

Benign

0.52

T;T

Polyphen

0.0

B;B

Vest4

0.11

MutPred

0.27

Gain of relative solvent accessibility (P = 0.1894);.;

MVP

0.24

MPC

0.18

ClinPred

0.11

GERP RS

-3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.053

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over