Variant 14-24182984-G-C 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_024658.4(IPO4):c.2413C>G(p.Gln805Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,852 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: 0.0000021 ( 0 hom. )

Consequence

IPO4
NM_024658.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.00

Variant links:

Genes affected

IPO4 (HGNC:19426): (importin 4) Predicted to enable nuclear import signal receptor activity and nuclear localization sequence binding activity. Involved in DNA replication-dependent chromatin assembly; DNA replication-independent chromatin assembly; and protein import into nucleus. Located in chromatin. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

IPO4 links:

ENSG00000259522 (HGNC:):

ENSG00000259522 links:

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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=0.15402842).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IPO4	NM_024658.4 link	c.2413C>G	p.Gln805Glu	missense_variant	23/30	ENST00000354464.11	NP_078934.3	Q8TEX9-1B3KT38
IPO4	NR_051979.2 link	n.2442C>G		non_coding_transcript_exon_variant	23/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IPO4	ENST00000354464.11 link	c.2413C>G	p.Gln805Glu	missense_variant	23/30	1	NM_024658.4	ENSP00000346453.6	Q8TEX9-1
ENSG00000259522	ENST00000561419.1 link	n.*3040C>G		non_coding_transcript_exon_variant	24/31	2		ENSP00000454374.1	H3BMG7
ENSG00000259522	ENST00000561419.1 link	n.*3040C>G		3_prime_UTR_variant	24/31	2		ENSP00000454374.1	H3BMG7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460852

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726570

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 12, 2022

The c.2413C>G (p.Q805E) alteration is located in exon 23 (coding exon 23) of the IPO4 gene. This alteration results from a C to G substitution at nucleotide position 2413, causing the glutamine (Q) at amino acid position 805 to be replaced by a glutamic acid (E). 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

0.11

BayesDel_addAF

Uncertain

0.052

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.095

Eigen

Benign

-0.18

Eigen_PC

Benign

0.039

FATHMM_MKL

Uncertain

0.77

M_CAP

Benign

0.011

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.70

REVEL

Benign

0.18

Sift

Benign

0.47

Sift4G

Benign

0.51

Polyphen

0.0010

Vest4

0.26

MutPred

0.32

Gain of ubiquitination at K801 (P = 0.0432);

MVP

0.63

MPC

0.25

ClinPred

0.66

GERP RS

5.0

Varity_R

0.45

gMVP

0.070

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

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