Variant chr8-21984688-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_015024.5(XPO7):c.1320G>C(p.Gln440His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

XPO7
NM_015024.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.894

Variant links:

Genes affected

XPO7 (HGNC:14108): (exportin 7) The transport of protein and large RNAs through the nuclear pore complexes (NPC) is an energy-dependent and regulated process. The import of proteins with a nuclear localization signal (NLS) is accomplished by recognition of one or more clusters of basic amino acids by the importin-alpha/beta complex; see MIM 600685 and MIM 602738. The small GTPase RAN (MIM 601179) plays a key role in NLS-dependent protein import. RAN-binding protein-16 is a member of the importin-beta superfamily of nuclear transport receptors.[supplied by OMIM, Jul 2002]

XPO7 links:

XPO7 (HGNC:):

XPO7 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), XPO7. . Gene score misZ 4.8157 (greater than the threshold 3.09). Trascript score misZ 5.4671 (greater than threshold 3.09). GenCC has associacion of gene with prostate cancer.

BP4

Computational evidence support a benign effect (MetaRNN=0.29627764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPO7	NM_015024.5 linkuse as main transcript	c.1320G>C	p.Gln440His	missense_variant	12/28	ENST00000252512.14	NP_055839.3	Q9UIA9
XPO7	NM_001100161.2 linkuse as main transcript	c.1347G>C	p.Gln449His	missense_variant	12/28		NP_001093631.1
XPO7	NM_001362802.2 linkuse as main transcript	c.1254G>C	p.Gln418His	missense_variant	11/27		NP_001349731.1
XPO7	NR_156173.2 linkuse as main transcript	n.1429G>C		non_coding_transcript_exon_variant	12/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPO7	ENST00000252512.14 linkuse as main transcript	c.1320G>C	p.Gln440His	missense_variant	12/28	1	NM_015024.5	ENSP00000252512.9		Q9UIA9
XPO7	ENST00000433566.8 linkuse as main transcript	c.1323G>C	p.Gln441His	missense_variant	12/28	5		ENSP00000410249.3		E7ESC6

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000827

AC:

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

Nov 10, 2022

The c.1320G>C (p.Q440H) alteration is located in exon 12 (coding exon 12) of the XPO7 gene. This alteration results from a G to C substitution at nucleotide position 1320, causing the glutamine (Q) at amino acid position 440 to be replaced by a histidine (H). 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

0.24

BayesDel_addAF

Benign

-0.018

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.27

T;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.23

Sift

Benign

0.58

T;T

Sift4G

Benign

0.22

T;T

Polyphen

0.025

B;B

Vest4

0.67

MVP

0.15

MPC

1.7

ClinPred

0.73

GERP RS

2.2

Varity_R

0.23

gMVP

0.59

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