8-21994445-A-G

Variant names:

• chr8-21994445-A-G
• NM_015024.5:c.2231A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015024.5(XPO7):​c.2231A>G​(p.Glu744Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: XPO7 NM_015024.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.07

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPO7	NM_015024.5	c.2231A>G	p.Glu744Gly	missense_variant	Exon 20 of 28	ENST00000252512.14	NP_055839.3
XPO7	NM_001100161.2	c.2258A>G	p.Glu753Gly	missense_variant	Exon 20 of 28		NP_001093631.1
XPO7	NM_001362802.2	c.2165A>G	p.Glu722Gly	missense_variant	Exon 19 of 27		NP_001349731.1
XPO7	NR_156173.2	n.2451A>G		non_coding_transcript_exon_variant	Exon 21 of 29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPO7	ENST00000252512.14	c.2231A>G	p.Glu744Gly	missense_variant	Exon 20 of 28	1	NM_015024.5	ENSP00000252512.9
XPO7	ENST00000433566.8	c.2234A>G	p.Glu745Gly	missense_variant	Exon 20 of 28	5		ENSP00000410249.3
XPO7	ENST00000517551.2	c.161A>G	p.Glu54Gly	missense_variant	Exon 2 of 6	5		ENSP00000429317.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2231A>G (p.E744G) alteration is located in exon 20 (coding exon 20) of the XPO7 gene. This alteration results from a A to G substitution at nucleotide position 2231, causing the glutamic acid (E) at amino acid position 744 to be replaced by a glycine (G). 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	Uncertain	0.46
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T;.;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T;T;D
M_CAP	Benign	0.080	D
MetaRNN	Uncertain	0.63	D;D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.2	M;.;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-4.0	D;D;D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		0.045	B;B;.
Vest4		0.61
MVP		0.093
MPC		0.69
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.43
gMVP		0.47

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.

Other links and lift over

hg19: chr8-21851956;