13-20796211-C-T

Variant names:

• chr13-20796211-C-T
• rs988867859
• NM_022459.5:c.2662G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022459.5(XPO4):​c.2662G>A​(p.Val888Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V888L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: XPO4 NM_022459.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.54
• Publications: 1 publications found

Genes affected

XPO4 (HGNC:17796): (exportin 4) XPO4 belongs to a large family of karyopherins (see MIM 602738) that mediate the transport of proteins and other cargo between the nuclear and cytoplasmic compartments (Lipowsky et al., 2000 [PubMed 10944119]).[supplied by OMIM, Mar 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3796262).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022459.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPO4	NM_022459.5	MANE Select	c.2662G>A	p.Val888Met	missense	Exon 18 of 23	NP_071904.4
	XPO4	NM_001372061.1		c.2662G>A	p.Val888Met	missense	Exon 18 of 20	NP_001358990.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPO4	ENST00000255305.11	TSL:1 MANE Select	c.2662G>A	p.Val888Met	missense	Exon 18 of 23	ENSP00000255305.6	Q9C0E2
	XPO4	ENST00000909777.1		c.2662G>A	p.Val888Met	missense	Exon 18 of 23	ENSP00000579836.1
	XPO4	ENST00000953408.1		c.2662G>A	p.Val888Met	missense	Exon 18 of 22	ENSP00000623467.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.040	T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		7.5
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.16
Sift	Benign	0.15	T
Sift4G	Uncertain	0.037	D
Polyphen		0.036	B
Vest4		0.59
MutPred		0.38		Gain of ubiquitination at K891 (P = 0.0825)
MVP		0.25
MPC		0.73
ClinPred		0.69	D
GERP RS		5.6
Varity_R		0.31
gMVP		0.55
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs988867859; hg19: chr13-21370350;