13-20796830-C-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_022459.5(XPO4):​c.2550G>T​(p.Glu850Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,790 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: 0.0000048 ( 0 hom. )

Consequence

XPO4
NM_022459.5 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.79
Variant links:
Genes affected
XPO4 (HGNC:17796): (exportin 4) XPO4 belongs to a large family of karyopherins (see MIM 602738) that mediate the transport of proteins and other cargo between the nuclear and cytoplasmic compartments (Lipowsky et al., 2000 [PubMed 10944119]).[supplied by OMIM, Mar 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.34118176).
BS2
High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
XPO4NM_022459.5 linkuse as main transcriptc.2550G>T p.Glu850Asp missense_variant 17/23 ENST00000255305.11 NP_071904.4 Q9C0E2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
XPO4ENST00000255305.11 linkuse as main transcriptc.2550G>T p.Glu850Asp missense_variant 17/231 NM_022459.5 ENSP00000255305.6 Q9C0E2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
249188
Hom.:
0
AF XY:
0.00000740
AC XY:
1
AN XY:
135204
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:
0.0000265
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461790
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727198
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000987
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.00000828
AC:
1

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 submitterclinical testingAmbry GeneticsSep 14, 2022The c.2550G>T (p.E850D) alteration is located in exon 17 (coding exon 17) of the XPO4 gene. This alteration results from a G to T substitution at nucleotide position 2550, causing the glutamic acid (E) at amino acid position 850 to be replaced by an aspartic acid (D). 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
0.10
BayesDel_addAF
Benign
-0.054
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
18
DANN
Benign
0.96
DEOGEN2
Benign
0.023
T;T
Eigen
Benign
-0.49
Eigen_PC
Benign
-0.30
FATHMM_MKL
Benign
0.75
D
LIST_S2
Uncertain
0.91
D;D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.34
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.49
N;.
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-0.25
N;N
REVEL
Benign
0.20
Sift
Benign
0.50
T;T
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.0080
B;.
Vest4
0.77
MutPred
0.36
Gain of ubiquitination at K846 (P = 0.1103);Gain of ubiquitination at K846 (P = 0.1103);
MVP
0.34
MPC
0.65
ClinPred
0.10
T
GERP RS
3.3
Varity_R
0.081
gMVP
0.26

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs772777457; hg19: chr13-21370969; API