Variant 16-28098561-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015171.4(XPO6):c.3355C>T(p.Pro1119Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,200 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

XPO6
NM_015171.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.91

Variant links:

Genes affected

XPO6 (HGNC:19733): (exportin 6) The protein encoded by this gene is a member of the importin-beta family. Members of this family are regulated by the GTPase Ran to mediate transport of cargo across the nuclear envelope. This protein has been shown to mediate nuclear export of profilin-actin complexes. A pseudogene of this gene is located on the long arm of chromosome 14. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Aug 2012]

XPO6 links:

LOC124903669 (HGNC:):

LOC124903669 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	UniProt
XPO6	NM_015171.4 linkuse as main transcript	c.3355C>T	p.Pro1119Ser	missense_variant	24/24	ENST00000304658.10	NP_055986.1	Q96QU8-1
XPO6	NM_001270940.2 linkuse as main transcript	c.3313C>T	p.Pro1105Ser	missense_variant	25/25		NP_001257869.1	Q96QU8-2
LOC124903669	XR_007065032.1 linkuse as main transcript	n.89+983G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
XPO6	ENST00000304658.10 linkuse as main transcript	c.3355C>T	p.Pro1119Ser	missense_variant	24/24	1	NM_015171.4	ENSP00000302790.4	Q96QU8-1
XPO6	ENST00000565698.5 linkuse as main transcript	c.3313C>T	p.Pro1105Ser	missense_variant	25/25	2		ENSP00000457341.1	Q96QU8-2
XPO6	ENST00000568065.5 linkuse as main transcript	c.376C>T	p.Pro126Ser	missense_variant	3/3	5		ENSP00000456422.1	H3BRV5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460200

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000166

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

Aug 10, 2024

The c.3355C>T (p.P1119S) alteration is located in exon 24 (coding exon 24) of the XPO6 gene. This alteration results from a C to T substitution at nucleotide position 3355, causing the proline (P) at amino acid position 1119 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

Pathogenic

0.84

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.23

.;.;T

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Uncertain

0.18

MetaRNN

Uncertain

0.62

D;D;D

MetaSVM

Uncertain

0.042

MutationAssessor

Uncertain

2.4

.;.;M

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-3.1

D;D;D

REVEL

Uncertain

0.44

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;.;D

Vest4

0.71

MutPred

0.29

.;.;Loss of catalytic residue at P1119 (P = 0.031);

MVP

0.28

MPC

1.7

ClinPred

0.99

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.56

gMVP

0.70

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