13-20796185-C-A

Variant names:

• chr13-20796185-C-A
• NM_022459.5:c.2688G>T
• XPO4 p.Arg896Arg

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_022459.5(XPO4):​c.2688G>T​(p.Arg896Arg) variant causes a synonymous change involving the alteration of a non-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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: XPO4 NM_022459.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.386
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP7: Synonymous conserved (PhyloP=0.386 with no splicing effect.

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.2688G>T	p.Arg896Arg	synonymous	Exon 18 of 23	NP_071904.4
	XPO4	NM_001372061.1		c.2688G>T	p.Arg896Arg	synonymous	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.2688G>T	p.Arg896Arg	synonymous	Exon 18 of 23	ENSP00000255305.6	Q9C0E2
	XPO4	ENST00000909777.1		c.2688G>T	p.Arg896Arg	synonymous	Exon 18 of 23	ENSP00000579836.1
	XPO4	ENST00000953408.1		c.2688G>T	p.Arg896Arg	synonymous	Exon 18 of 22	ENSP00000623467.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	6.7
DANN	Benign	0.62
PhyloP100		0.39

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr13-21370324;