16-28146112-T-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_015171.4(XPO6):c.1316A>T(p.Lys439Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,613,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
XPO6
NM_015171.4 missense
NM_015171.4 missense
Scores
8
8
Clinical Significance
Conservation
PhyloP100: 3.41
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, XPO6
BP4
?
Computational evidence support a benign effect (MetaRNN=0.1344651).
BS2
?
High AC in GnomAd at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XPO6 | NM_015171.4 | c.1316A>T | p.Lys439Met | missense_variant | 9/24 | ENST00000304658.10 | |
XPO6 | NM_001270940.2 | c.1274A>T | p.Lys425Met | missense_variant | 10/25 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XPO6 | ENST00000304658.10 | c.1316A>T | p.Lys439Met | missense_variant | 9/24 | 1 | NM_015171.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152232Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000241 AC: 6AN: 249394Hom.: 0 AF XY: 0.0000443 AC XY: 6AN XY: 135308
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461550Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9AN XY: 727102
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GnomAD4 genome ? AF: 0.0000920 AC: 14AN: 152232Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74370
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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 | Sep 14, 2023 | The c.1316A>T (p.K439M) alteration is located in exon 9 (coding exon 9) of the XPO6 gene. This alteration results from a A to T substitution at nucleotide position 1316, causing the lysine (K) at amino acid position 439 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
0.79
.;P
Vest4
MutPred
0.36
.;Loss of ubiquitination at K439 (P = 0.0074);
MVP
MPC
1.1
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at