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Intellectual Disability (Syndromic and Non-Syndromic) via the UPF3B Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
UPF3B 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9927UPF3B81479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Renee Bend, PhD

Clinical Features and Genetics

Clinical Features

Intellectual Disability (ID) is a heterogeneous group of disorders, characterized by congenital limitation in intellectual functioning (intelligence quotient, IQ below 70) and adaptive behavior, diagnosed in ~1–3% of the population before 18 years of age. ID can be presented as isolated cases (non-syndromic ID) or in combination with other malformations, dysmorphic features, and/or neurological abnormalities (syndromic ID). X-linked Intellectual Disability (XLID) contributes almost 10-15% of the ID cases in males, and non-syndromic XLID is more prevalent as it accounts for almost two third of the XLID cases (de Brouwer et al. 2007). Pathogenic variants in the UPF3B gene have been reported in several families with syndromic and non-syndromic XLID. The common clinical features of UPF3B-related syndromic XLID includes mild to severe intellectual disability with autistic features, slender build, poor musculature, long face, high-arched palate and pectus deformities, sometimes childhood-onset schizophrenia and/or attention deficit hyperactivity disorder (Tarpey et al. 2009; Jolly et al. 2013). UPF3B (Regulator of nonsense transcripts 3B) is a cytosolic protein and a part of a post-splicing multiprotein complex that is involved in the nonsense-mediated mRNA decay (NMD) pathway. Interestingly, the NMD pathway has recently been linked with neuronal differentiation and axon guidance (Colak et al. 2013), and pathogenic alterations in the NMD genes have been implicated in neurodevelopmental disorders (Nguyen et al. 2013).


UPF3B-related intellectual disability is inherited in X-linked recessive manner. Loss-of-function pathogenic variants in UPF3B result in neurodevelopmental disorders with variable clinical presentations, including syndromic and non-syndromic intellectual disability (Jolly et al. 2013). UPF3B is a core member of the highly conserved nonsense-mediated mRNA decay (NMD) pathway which is involved in the rapid degradation of transcripts with premature termination codons, as well as mRNA stability and regulation of gene expression (Alrahbeni et al. 2015). UPF3B consists of 11 exons and encodes a 483 amino acid polypeptide. Nonsense and missense pathogenic variants, as well as small deletions, have been reported in UPF3B.

Clinical Sensitivity - Sequencing with CNV PGxome

This test is predicted to detect pathogenic variants in <0.1% of individuals with intellectual disability (ID). In this context, it is important to note that although pathological variants in over 700 genes have been identified in individuals with ID, a genetic diagnosis is still lacking in most cases due to extreme clinical and genetic heterogeneity (Vissers et al. 2016). Analytical sensitivity should be high because all pathogenic variants reported to date are detectable by sequencing.

To date, there is no report of any large deletion or duplication involving this gene.

Testing Strategy

This test provides full coverage of all coding exons of the UPF3B gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

This test is primarily indicated for the patients with mild to severe intellectual disabilities (both syndromic and non-syndromic) who are negative for any kind of cytogenetic abnormalities, copy number variations, and Fragile-X syndrome and also for the family members of the patients who have UPF3B pathogenic variants. Prenatal diagnosis is possible if the genetic diagnosis has been firmly established in an affected family member.


Official Gene Symbol OMIM ID
UPF3B 300298
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Mental Retardation, X-Linked, Syndromic 14 XL 300676


  • Alrahbeni T. et al. 2015. Molecular Brain. 8: 33. PubMed ID: 26012578
  • Colak D. et al. 2013. Cell. 153: 1252-65. PubMed ID: 23746841
  • de Brouwer A.P. et al. 2007. Human Mutation. 28: 207-8. PubMed ID: 17221867
  • Jolly L.A. et al. 2013.Human Molecular Genetics. 22: 4673-87. PubMed ID: 23821644
  • Nguyen L.S. et al. 2013. Human Molecular Genetics. 22: 1816-25. PubMed ID: 23376982
  • Tarpey P.S. et al. 2009. Nature Genetics. 41: 535-43. PubMed ID: 19377476
  • Vissers L.E. et al. 2016. Nature Reviews. Genetics. 17: 9-18. PubMed ID: 26503795


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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2) Select Additional Test Options

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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