GeneBe

rs55712755

Variant names:

Variant summary

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

The NM_080632.3(UPF3B):​c.263+12_263+18delAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000202 in 495,915 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)
Exomes 𝑓: 0.0000020 ( 0 hom. 0 hem. )

Consequence

UPF3B
NM_080632.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.277

Publications

0 publications found
Variant links:
Genes affected
UPF3B (HGNC:20439): (UPF3B regulator of nonsense mediated mRNA decay) This gene encodes a protein that is part of a post-splicing multiprotein complex involved in both mRNA nuclear export and mRNA surveillance. The encoded protein is one of two functional homologs to yeast Upf3p. mRNA surveillance detects exported mRNAs with truncated open reading frames and initiates nonsense-mediated mRNA decay (NMD). When translation ends upstream from the last exon-exon junction, this triggers NMD to degrade mRNAs containing premature stop codons. This protein binds to the mRNA and remains bound after nuclear export, acting as a nucleocytoplasmic shuttling protein. It forms with Y14 a complex that binds specifically 20 nt upstream of exon-exon junctions. This gene is located on the long arm of chromosome X. Two splice variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
UPF3B Gene-Disease associations (from GenCC):
  • syndromic X-linked intellectual disability 14
    Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
  • X-linked complex neurodevelopmental disorder
    Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
  • non-syndromic X-linked intellectual disability
    Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
  • X-linked intellectual disability with marfanoid habitus
    Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

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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;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UPF3BNM_080632.3 linkc.263+12_263+18delAAAAAAA intron_variant Intron 2 of 10 ENST00000276201.7 NP_542199.1 Q9BZI7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UPF3BENST00000276201.7 linkc.263+12_263+18delAAAAAAA intron_variant Intron 2 of 10 1 NM_080632.3 ENSP00000276201.3 Q9BZI7-1
UPF3BENST00000345865.6 linkc.263+12_263+18delAAAAAAA intron_variant Intron 2 of 9 1 ENSP00000245418.2 Q9BZI7-2

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
AF:
0.00000202
AC:
1
AN:
495915
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
146101
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
7492
American (AMR)
AF:
0.00
AC:
0
AN:
12191
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
11429
East Asian (EAS)
AF:
0.00
AC:
0
AN:
15069
South Asian (SAS)
AF:
0.00
AC:
0
AN:
28814
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
26364
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
1586
European-Non Finnish (NFE)
AF:
0.00000270
AC:
1
AN:
370545
Other (OTH)
AF:
0.00
AC:
0
AN:
22425
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
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.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.28

Splicing

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

Publications

Other links and lift over

dbSNP: rs55712755; hg19: chrX-118985711; API