Variant 14-24181797-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_024658.4(IPO4):c.2854G>A(p.Glu952Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,446,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

IPO4
NM_024658.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.36

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:

IPO4 (HGNC:):

IPO4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.838

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IPO4	NM_024658.4 linkuse as main transcript	c.2854G>A	p.Glu952Lys	missense_variant	27/30	ENST00000354464.11	NP_078934.3	Q8TEX9-1B3KT38
IPO4	NR_051979.2 linkuse as main transcript	n.2903G>A		non_coding_transcript_exon_variant	27/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IPO4	ENST00000354464.11 linkuse as main transcript	c.2854G>A	p.Glu952Lys	missense_variant	27/30	1	NM_024658.4	ENSP00000346453.6	Q8TEX9-1
ENSG00000259522	ENST00000561419.1 linkuse as main transcript	n.*3481G>A		non_coding_transcript_exon_variant	28/31	2		ENSP00000454374.1	H3BMG7
ENSG00000259522	ENST00000561419.1 linkuse as main transcript	n.*3481G>A		3_prime_UTR_variant	28/31	2		ENSP00000454374.1	H3BMG7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1446908

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717778

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:

0.0000190

Gnomad4 NFE exome

AF:

0.00

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

May 14, 2024

The c.2854G>A (p.E952K) alteration is located in exon 27 (coding exon 27) of the IPO4 gene. This alteration results from a G to A substitution at nucleotide position 2854, causing the glutamic acid (E) at amino acid position 952 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

Pathogenic

0.84

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.50

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.020

MetaRNN

Pathogenic

0.84

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.6

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.26

Sift

Uncertain

0.0060

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.76

MutPred

0.60

Gain of MoRF binding (P = 0.0015);

MVP

0.63

MPC

0.88

ClinPred

0.98

GERP RS

6.0

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.1

Varity_R

0.81

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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