12-64430205-T-G

Position:

• chr12-64430205-T-G

Variant summary

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

The NM_007235.6(XPOT):​c.1894T>G​(p.Leu632Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: XPOT NM_007235.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.70

Genes affected

XPOT (HGNC:12826): (exportin for tRNA) This gene encodes a protein belonging to the RAN-GTPase exportin family that mediates export of tRNA from the nucleus to the cytoplasm. Translocation of tRNA to the cytoplasm occurs once exportin has bound both tRNA and GTP-bound RAN. [provided by RefSeq, Jul 2008]

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/exons	MANE	Protein	UniProt
XPOT	NM_007235.6	c.1894T>G	p.Leu632Val	missense_variant	17/25	ENST00000332707.10	NP_009166.2
XPOT	XM_017018748.2	c.1894T>G	p.Leu632Val	missense_variant	17/25		XP_016874237.1
XPOT	XM_047428193.1	c.1894T>G	p.Leu632Val	missense_variant	17/25		XP_047284149.1
XPOT	XM_047428195.1	c.460T>G	p.Leu154Val	missense_variant	6/14		XP_047284151.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPOT	ENST00000332707.10	c.1894T>G	p.Leu632Val	missense_variant	17/25	2	NM_007235.6	ENSP00000327821	P1
XPOT	ENST00000541842.1	n.518T>G		non_coding_transcript_exon_variant	3/3	2
XPOT	ENST00000542958.5	n.932T>G		non_coding_transcript_exon_variant	6/8	5
XPOT	ENST00000538086.5	c.*371T>G		3_prime_UTR_variant, NMD_transcript_variant	6/7	5		ENSP00000444345

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 12, 2023

The c.1894T>G (p.L632V) alteration is located in exon 17 (coding exon 16) of the XPOT gene. This alteration results from a T to G substitution at nucleotide position 1894, causing the leucine (L) at amino acid position 632 to be replaced by a valine (V). 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	0.14
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.12
Sift	Benign	0.035	D
Sift4G	Uncertain	0.039	D
Polyphen		0.98	D
Vest4		0.74
MutPred		0.40		Gain of catalytic residue at M636 (P = 0.0156);
MVP		0.40
MPC		1.0
ClinPred		0.77	D
GERP RS		5.3
Varity_R		0.20
gMVP		0.43

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: chr12-64823985;