16-28156468-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.703A>T(p.Ile235Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000274 in 1,607,720 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000028 ( 1 hom. )
Consequence
XPO6
NM_015171.4 missense
NM_015171.4 missense
Scores
1
3
12
Clinical Significance
Conservation
PhyloP100: 5.67
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=0.22186017).
BS2
?
High AC in GnomAdExome at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XPO6 | NM_015171.4 | c.703A>T | p.Ile235Phe | missense_variant | 7/24 | ENST00000304658.10 | |
XPO6 | NM_001270940.2 | c.661A>T | p.Ile221Phe | missense_variant | 8/25 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XPO6 | ENST00000304658.10 | c.703A>T | p.Ile235Phe | missense_variant | 7/24 | 1 | NM_015171.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152100Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000325 AC: 8AN: 246050Hom.: 0 AF XY: 0.0000375 AC XY: 5AN XY: 133386
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GnomAD4 exome AF: 0.0000282 AC: 41AN: 1455620Hom.: 1 Cov.: 31 AF XY: 0.0000360 AC XY: 26AN XY: 723102
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152100Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74304
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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 27, 2021 | The c.703A>T (p.I235F) alteration is located in exon 7 (coding exon 7) of the XPO6 gene. This alteration results from a A to T substitution at nucleotide position 703, causing the isoleucine (I) at amino acid position 235 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
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
Benign
T;T
Sift4G
Benign
T;T
Polyphen
0.49
.;P
Vest4
MutPred
0.45
.;Loss of helix (P = 0.1299);
MVP
MPC
1.7
ClinPred
T
GERP RS
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