rs189823406

Variant names:

• chr8-21970193-C-G
• rs189823406
• NM_015024.5:c.309C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-21970193-C-G
• chr8-21970193-C-T

Variant summary

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

The NM_015024.5(XPO7):​c.309C>G​(p.Phe103Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,350 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: XPO7 NM_015024.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

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.309C>G	p.Phe103Leu	missense_variant	Exon 4 of 28	ENST00000252512.14	NP_055839.3
XPO7	NM_001100161.2	c.309C>G	p.Phe103Leu	missense_variant	Exon 4 of 28		NP_001093631.1
XPO7	NM_001362802.2	c.309C>G	p.Phe103Leu	missense_variant	Exon 4 of 27		NP_001349731.1
XPO7	NR_156173.2	n.418C>G		non_coding_transcript_exon_variant	Exon 4 of 29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPO7	ENST00000252512.14	c.309C>G	p.Phe103Leu	missense_variant	Exon 4 of 28	1	NM_015024.5	ENSP00000252512.9
XPO7	ENST00000518017.1	n.504C>G		non_coding_transcript_exon_variant	Exon 4 of 7	1
XPO7	ENST00000433566.8	c.312C>G	p.Phe104Leu	missense_variant	Exon 4 of 28	5		ENSP00000410249.3
XPO7	ENST00000521303.5	c.321C>G	p.Phe107Leu	missense_variant	Exon 4 of 6	5		ENSP00000429290.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461350 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726952

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.084	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	1.9
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T;.
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.37	N
LIST_S2	Uncertain	0.94	D;D
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Uncertain	0.066	D
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-4.8	D;D
REVEL	Uncertain	0.39
Sift	Benign	0.036	D;D
Sift4G	Uncertain	0.058	T;T
Polyphen		0.61	P;B
Vest4		0.86
MutPred		0.57		Gain of ubiquitination at K99 (P = 0.1797);.;
MVP		0.39
MPC		1.5
ClinPred		0.93	D
GERP RS		-5.3
Varity_R		0.54
gMVP		0.77

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

LitVar

Other links and lift over

dbSNP: rs189823406; hg19: chr8-21827704;