chr16-28166511-T-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_015171.4(XPO6):c.640A>T(p.Ser214Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000139 in 1,585,662 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
XPO6
NM_015171.4 missense
NM_015171.4 missense
Scores
1
10
5
Clinical Significance
Conservation
PhyloP100: 4.51
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, XPO6
BS2
?
High AC in GnomAd at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XPO6 | NM_015171.4 | c.640A>T | p.Ser214Cys | missense_variant | 6/24 | ENST00000304658.10 | |
XPO6 | NM_001270940.2 | c.598A>T | p.Ser200Cys | missense_variant | 7/25 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XPO6 | ENST00000304658.10 | c.640A>T | p.Ser214Cys | missense_variant | 6/24 | 1 | NM_015171.4 | P1 | |
XPO6 | ENST00000565698.5 | c.598A>T | p.Ser200Cys | missense_variant | 7/25 | 2 | |||
XPO6 | ENST00000574435.1 | c.152+3239A>T | intron_variant | 5 | |||||
XPO6 | ENST00000573645.1 | n.293A>T | non_coding_transcript_exon_variant | 3/4 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000461 AC: 7AN: 152004Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
7
AN:
152004
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000145 AC: 3AN: 206452Hom.: 0 AF XY: 0.0000181 AC XY: 2AN XY: 110720
GnomAD3 exomes
AF:
AC:
3
AN:
206452
Hom.:
AF XY:
AC XY:
2
AN XY:
110720
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000105 AC: 15AN: 1433658Hom.: 0 Cov.: 31 AF XY: 0.0000113 AC XY: 8AN XY: 710162
GnomAD4 exome
AF:
AC:
15
AN:
1433658
Hom.:
Cov.:
31
AF XY:
AC XY:
8
AN XY:
710162
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000461 AC: 7AN: 152004Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74258
GnomAD4 genome
?
AF:
AC:
7
AN:
152004
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74258
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
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 | Apr 25, 2022 | The c.640A>T (p.S214C) alteration is located in exon 6 (coding exon 6) of the XPO6 gene. This alteration results from a A to T substitution at nucleotide position 640, causing the serine (S) at amino acid position 214 to be replaced by a cysteine (C). 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
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
0.99
.;D
Vest4
MVP
MPC
1.5
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at