Variant 12-64414968-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_007235.6(XPOT):c.122C>G(p.Ala41Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,606 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

XPOT
NM_007235.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.58

Variant links:

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]

XPOT links:

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ACMG classification

Classification made for transcript

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
XPOT	NM_007235.6 linkuse as main transcript	c.122C>G	p.Ala41Gly	missense_variant	3/25	ENST00000332707.10	NP_009166.2
XPOT	XM_017018748.2 linkuse as main transcript	c.122C>G	p.Ala41Gly	missense_variant	3/25		XP_016874237.1
XPOT	XM_047428193.1 linkuse as main transcript	c.122C>G	p.Ala41Gly	missense_variant	3/25		XP_047284149.1
XPOT	XM_047428194.1 linkuse as main transcript	c.122C>G	p.Ala41Gly	missense_variant	3/15		XP_047284150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
XPOT	ENST00000332707.10 linkuse as main transcript	c.122C>G	p.Ala41Gly	missense_variant	3/25	2	NM_007235.6	ENSP00000327821	P1
XPOT	ENST00000400935.2 linkuse as main transcript	c.122C>G	p.Ala41Gly	missense_variant	2/6	2		ENSP00000383722
XPOT	ENST00000540203.5 linkuse as main transcript	c.122C>G	p.Ala41Gly	missense_variant	3/4	4		ENSP00000441376

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460606

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726656

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.122C>G (p.A41G) alteration is located in exon 3 (coding exon 2) of the XPOT gene. This alteration results from a C to G substitution at nucleotide position 122, causing the alanine (A) at amino acid position 41 to be replaced by a glycine (G). 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

0.29

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

T;T;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.039

MetaRNN

Uncertain

0.56

D;D;D

MetaSVM

Benign

-0.73

MutationAssessor

Benign

2.0

M;.;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-2.0

N;D;N

REVEL

Uncertain

0.33

Sift

Benign

0.054

T;T;T

Sift4G

Uncertain

0.026

D;D;D

Polyphen

0.42

B;.;.

Vest4

0.75

MutPred

0.56

Gain of catalytic residue at E40 (P = 0.0028);Gain of catalytic residue at E40 (P = 0.0028);Gain of catalytic residue at E40 (P = 0.0028);

MVP

0.29

MPC

0.51

ClinPred

0.80

GERP RS

5.5

Varity_R

0.25

gMVP

0.40

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over