Variant 8-21994426-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_015024.5(XPO7):c.2212A>C(p.Ser738Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,872 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

XPO7
NM_015024.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.07

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPO7	NM_015024.5 link	c.2212A>C	p.Ser738Arg	missense_variant	Exon 20 of 28	ENST00000252512.14	NP_055839.3	Q9UIA9
XPO7	NM_001100161.2 link	c.2239A>C	p.Ser747Arg	missense_variant	Exon 20 of 28		NP_001093631.1
XPO7	NM_001362802.2 link	c.2146A>C	p.Ser716Arg	missense_variant	Exon 19 of 27		NP_001349731.1
XPO7	NR_156173.2 link	n.2432A>C		non_coding_transcript_exon_variant	Exon 21 of 29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
XPO7	ENST00000252512.14 link	c.2212A>C	p.Ser738Arg	missense_variant	Exon 20 of 28	1	NM_015024.5	ENSP00000252512.9	Q9UIA9
XPO7	ENST00000433566.8 link	c.2215A>C	p.Ser739Arg	missense_variant	Exon 20 of 28	5		ENSP00000410249.3	E7ESC6
XPO7	ENST00000517551.2 link	c.142A>C	p.Ser48Arg	missense_variant	Exon 2 of 6	5		ENSP00000429317.2	E5RIW1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248812

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134978

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:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1459872

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726136

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:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

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

Jan 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2212A>C (p.S738R) alteration is located in exon 20 (coding exon 20) of the XPO7 gene. This alteration results from a A to C substitution at nucleotide position 2212, causing the serine (S) at amino acid position 738 to be replaced by an arginine (R). 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

0.99

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;.;T

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.70

D;D;D

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.5

M;.;.

PrimateAI

Pathogenic

0.92

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Uncertain

0.57

Sift

Uncertain

0.017

D;D;D

Sift4G

Uncertain

0.015

D;D;D

Polyphen

0.86

P;D;.

Vest4

0.91

MVP

0.29

MPC

1.4

ClinPred

0.94

GERP RS

5.7

Varity_R

0.64

gMVP

0.83

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