8-21999172-C-T

Variant names:

• chr8-21999172-C-T
• rs1286959063
• NM_015024.5:c.2510C>T

Variant summary

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

The NM_015024.5(XPO7):​c.2510C>T​(p.Ser837Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: XPO7 NM_015024.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91

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.2510C>T	p.Ser837Phe	missense_variant	Exon 23 of 28	ENST00000252512.14	NP_055839.3
XPO7	NM_001100161.2	c.2537C>T	p.Ser846Phe	missense_variant	Exon 23 of 28		NP_001093631.1
XPO7	NM_001362802.2	c.2444C>T	p.Ser815Phe	missense_variant	Exon 22 of 27		NP_001349731.1
XPO7	NR_156173.2	n.2730C>T		non_coding_transcript_exon_variant	Exon 24 of 29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPO7	ENST00000252512.14	c.2510C>T	p.Ser837Phe	missense_variant	Exon 23 of 28	1	NM_015024.5	ENSP00000252512.9
XPO7	ENST00000433566.8	c.2513C>T	p.Ser838Phe	missense_variant	Exon 23 of 28	5		ENSP00000410249.3
XPO7	ENST00000517551.2	c.440C>T	p.Ser147Phe	missense_variant	Exon 5 of 6	5		ENSP00000429317.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;.;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.4	M;.;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-4.1	D;D;.
REVEL	Uncertain	0.42
Sift	Uncertain	0.022	D;D;.
Sift4G	Uncertain	0.033	D;D;D
Polyphen		0.068	B;P;.
Vest4		0.71
MVP		0.15
MPC		0.57
ClinPred		0.96	D
GERP RS		5.8
Varity_R		0.41
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

Other links and lift over

dbSNP: rs1286959063; hg19: chr8-21856683;