8-21969547-C-G

Position:

• chr8-21969547-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_015024.5(XPO7):​c.230C>G​(p.Pro77Arg) 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: 32)
• Consequence: XPO7 NM_015024.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.48

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 3 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPO7	NM_015024.5	c.230C>G	p.Pro77Arg	missense_variant	3/28	ENST00000252512.14	NP_055839.3
XPO7	NM_001100161.2	c.230C>G	p.Pro77Arg	missense_variant	3/28		NP_001093631.1
XPO7	NM_001362802.2	c.230C>G	p.Pro77Arg	missense_variant	3/27		NP_001349731.1
XPO7	NR_156173.2	n.339C>G		non_coding_transcript_exon_variant	3/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPO7	ENST00000252512.14	c.230C>G	p.Pro77Arg	missense_variant	3/28	1	NM_015024.5	ENSP00000252512.9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Jan 29, 2024

The c.230C>G (p.P77R) alteration is located in exon 3 (coding exon 3) of the XPO7 gene. This alteration results from a C to G substitution at nucleotide position 230, causing the proline (P) at amino acid position 77 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	0.57
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.092	T;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.061	D
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.8	N;N
REVEL	Uncertain	0.38
Sift	Benign	0.085	T;T
Sift4G	Benign	0.40	T;T
Polyphen		0.45	B;P
Vest4		0.81
MutPred		0.51		Gain of MoRF binding (P = 0.0322);.;
MVP		0.19
MPC		1.9
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.14
gMVP		0.57

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: chr8-21827058;