chr13-20790537-T-A

Position:

• chr13-20790537-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022459.5(XPO4):​c.2841A>T​(p.Arg947Ser) variant causes a missense 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: XPO4 NM_022459.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0710

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26350737).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPO4	NM_022459.5	c.2841A>T	p.Arg947Ser	missense_variant	19/23	ENST00000255305.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPO4	ENST00000255305.11	c.2841A>T	p.Arg947Ser	missense_variant	19/23	1	NM_022459.5	P1

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

Dec 14, 2021

The c.2841A>T (p.R947S) alteration is located in exon 19 (coding exon 19) of the XPO4 gene. This alteration results from a A to T substitution at nucleotide position 2841, causing the arginine (R) at amino acid position 947 to be replaced by a serine (S). 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	Benign	0.32
BayesDel_addAF	Benign	0.0037	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	T;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.49
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.030	N;N
REVEL	Benign	0.21
Sift	Benign	0.11	T;T
Sift4G	Benign	0.24	T;T
Polyphen		0.038	B;.
Vest4		0.67
MutPred		0.33		Gain of disorder (P = 0.0477);Gain of disorder (P = 0.0477);
MVP		0.29
MPC		0.82
ClinPred		0.47	T
GERP RS		1.8
Varity_R		0.16
gMVP		0.53

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: chr13-21364676;