GeneBe

rs368583529

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020750.3(XPO5):​c.3477+110_3477+118delTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 974,862 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: 26)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

XPO5
NM_020750.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.65

Publications

0 publications found
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]
POLR1C Gene-Disease associations (from GenCC):
  • hypomyelinating leukodystrophy 11
    Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • Treacher Collins syndrome 3
    Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
  • Treacher-Collins syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020750.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
XPO5
NM_020750.3
MANE Select
c.3477+110_3477+118delTTTTTTTTT
intron
N/ANP_065801.1Q9HAV4
POLR1C
NM_001318876.2
c.922+3315_922+3323delAAAAAAAAA
intron
N/ANP_001305805.1O15160-2
POLR1C
NM_001363658.2
c.922+3315_922+3323delAAAAAAAAA
intron
N/ANP_001350587.1A0A2R8YEZ4

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
XPO5
ENST00000265351.12
TSL:1 MANE Select
c.3477+110_3477+118delTTTTTTTTT
intron
N/AENSP00000265351.7Q9HAV4
POLR1C
ENST00000304004.7
TSL:1
c.922+3305_922+3313delAAAAAAAAA
intron
N/AENSP00000307212.3O15160-2
XPO5
ENST00000943409.1
c.3474+110_3474+118delTTTTTTTTT
intron
N/AENSP00000613468.1

Frequencies

GnomAD3 genomes
Cov.:
26
GnomAD4 exome
AF:
0.00000205
AC:
2
AN:
974862
Hom.:
0
AF XY:
0.00000209
AC XY:
1
AN XY:
479124
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
21400
American (AMR)
AF:
0.00
AC:
0
AN:
16318
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
15870
East Asian (EAS)
AF:
0.00
AC:
0
AN:
30234
South Asian (SAS)
AF:
0.00
AC:
0
AN:
49660
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
31754
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2862
European-Non Finnish (NFE)
AF:
0.00000262
AC:
2
AN:
764772
Other (OTH)
AF:
0.00
AC:
0
AN:
41992
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs368583529; hg19: chr6-43492090; API