8-21990398-C-G

Position:

• chr8-21990398-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_015024.5(XPO7):​c.1923C>G​(p.Asn641Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: XPO7 NM_015024.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.80

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 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=0.21247387).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPO7	NM_015024.5	c.1923C>G	p.Asn641Lys	missense_variant	17/28	ENST00000252512.14	NP_055839.3
XPO7	NM_001100161.2	c.1950C>G	p.Asn650Lys	missense_variant	17/28		NP_001093631.1
XPO7	NM_001362802.2	c.1857C>G	p.Asn619Lys	missense_variant	16/27		NP_001349731.1
XPO7	NR_156173.2	n.2143C>G		non_coding_transcript_exon_variant	18/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPO7	ENST00000252512.14	c.1923C>G	p.Asn641Lys	missense_variant	17/28	1	NM_015024.5	ENSP00000252512.9
XPO7	ENST00000433566.8	c.1926C>G	p.Asn642Lys	missense_variant	17/28	5		ENSP00000410249.3
XPO7	ENST00000518808.1	n.791C>G		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2023

The c.1923C>G (p.N641K) alteration is located in exon 17 (coding exon 17) of the XPO7 gene. This alteration results from a C to G substitution at nucleotide position 1923, causing the asparagine (N) at amino acid position 641 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	Benign	0.32
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.068
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.90	L;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.092
Sift	Benign	0.48	T;T
Sift4G	Benign	0.91	T;T
Polyphen		0.0020	B;B
Vest4		0.47
MVP		0.068
MPC		0.58
ClinPred		0.72	D
GERP RS		5.2
Varity_R		0.47
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: chr8-21847909;