Menu
GeneBe

rs2257082

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020750.3(XPO5):c.3303C>T(p.Tyr1101=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 1,612,466 control chromosomes in the GnomAD database, including 67,186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5882 hom., cov: 32)
Exomes 𝑓: 0.28 ( 61304 hom. )

Consequence

XPO5
NM_020750.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.280
Variant links:
Genes affected
XPO5 (HGNC:17675): (exportin 5) This gene encodes a member of the karyopherin family that is required for the transport of small RNAs and double-stranded RNA-binding proteins from the nucleus to the cytoplasm. The encoded protein translocates cargo through the nuclear pore complex in a RanGTP-dependent process. [provided by RefSeq, Aug 2011]
POLR1C (HGNC:20194): (RNA polymerase I and III subunit C) The protein encoded by this gene is a subunit of both RNA polymerase I and RNA polymerase III complexes. The encoded protein is part of the Pol core element. Mutations in this gene have been associated with Treacher Collins syndrome (TCS) and hypomyelinating leukodystrophy 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 6-43524840-G-A is Benign according to our data. Variant chr6-43524840-G-A is described in ClinVar as [Benign]. Clinvar id is 1262421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.28 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
XPO5NM_020750.3 linkuse as main transcriptc.3303C>T p.Tyr1101= synonymous_variant 30/32 ENST00000265351.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
XPO5ENST00000265351.12 linkuse as main transcriptc.3303C>T p.Tyr1101= synonymous_variant 30/321 NM_020750.3 P1

Frequencies

GnomAD3 genomes
AF:
0.265
AC:
40080
AN:
151340
Hom.:
5873
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.178
Gnomad AMI
AF:
0.316
Gnomad AMR
AF:
0.278
Gnomad ASJ
AF:
0.288
Gnomad EAS
AF:
0.622
Gnomad SAS
AF:
0.282
Gnomad FIN
AF:
0.328
Gnomad MID
AF:
0.259
Gnomad NFE
AF:
0.274
Gnomad OTH
AF:
0.272
GnomAD3 exomes
AF:
0.300
AC:
74602
AN:
248854
Hom.:
12538
AF XY:
0.297
AC XY:
40112
AN XY:
135022
show subpopulations
Gnomad AFR exome
AF:
0.170
Gnomad AMR exome
AF:
0.299
Gnomad ASJ exome
AF:
0.291
Gnomad EAS exome
AF:
0.635
Gnomad SAS exome
AF:
0.283
Gnomad FIN exome
AF:
0.333
Gnomad NFE exome
AF:
0.264
Gnomad OTH exome
AF:
0.287
GnomAD4 exome
AF:
0.282
AC:
412288
AN:
1461014
Hom.:
61304
Cov.:
39
AF XY:
0.282
AC XY:
204789
AN XY:
726822
show subpopulations
Gnomad4 AFR exome
AF:
0.167
Gnomad4 AMR exome
AF:
0.297
Gnomad4 ASJ exome
AF:
0.290
Gnomad4 EAS exome
AF:
0.615
Gnomad4 SAS exome
AF:
0.279
Gnomad4 FIN exome
AF:
0.329
Gnomad4 NFE exome
AF:
0.271
Gnomad4 OTH exome
AF:
0.291
GnomAD4 genome
AF:
0.265
AC:
40108
AN:
151452
Hom.:
5882
Cov.:
32
AF XY:
0.269
AC XY:
19939
AN XY:
74060
show subpopulations
Gnomad4 AFR
AF:
0.178
Gnomad4 AMR
AF:
0.278
Gnomad4 ASJ
AF:
0.288
Gnomad4 EAS
AF:
0.622
Gnomad4 SAS
AF:
0.282
Gnomad4 FIN
AF:
0.328
Gnomad4 NFE
AF:
0.274
Gnomad4 OTH
AF:
0.281
Alfa
AF:
0.269
Hom.:
13239
Bravo
AF:
0.257
Asia WGS
AF:
0.456
AC:
1588
AN:
3478
EpiCase
AF:
0.264
EpiControl
AF:
0.254

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -
Benign, criteria provided, single submitterclinical testingGeneDxJul 09, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.68
Cadd
Benign
4.9
Dann
Benign
0.74
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2257082; hg19: chr6-43492578; COSMIC: COSV54830091; COSMIC: COSV54830091; API