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When a Synonymous Variant Is Nonsynonymous

Vihinen, Mauno LU orcid (2022) In Genes 13(8).
Abstract

Term synonymous variation is widely used, but frequently in a wrong or misleading meaning and context. Twenty three point eight % of possible nucleotide substitution types in the universal genetic code are for synonymous amino acid changes, but when these variants have a phenotype and functional effect, they are very seldom synonymous. Such variants may manifest changes at DNA, RNA and/or protein levels. Large numbers of variations are erroneously annotated as synonymous, which causes problems e.g., in clinical genetics and diagnosis of diseases. To facilitate precise communication, novel systematics and nomenclature are introduced for variants that when looking only at the genetic code seem like synonymous, but which have phenotypes. A... (More)

Term synonymous variation is widely used, but frequently in a wrong or misleading meaning and context. Twenty three point eight % of possible nucleotide substitution types in the universal genetic code are for synonymous amino acid changes, but when these variants have a phenotype and functional effect, they are very seldom synonymous. Such variants may manifest changes at DNA, RNA and/or protein levels. Large numbers of variations are erroneously annotated as synonymous, which causes problems e.g., in clinical genetics and diagnosis of diseases. To facilitate precise communication, novel systematics and nomenclature are introduced for variants that when looking only at the genetic code seem like synonymous, but which have phenotypes. A new term, unsense variant is defined as a substitution in the mRNA coding region that affects gene expression and protein production without introducing a stop codon in the variation site. Such variants are common and need to be correctly annotated. Proper naming and annotation are important also to increase awareness of these variants and their consequences.

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Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
annotation, mutation, synonymous variation, terminology, variation interpretation, variation naming
in
Genes
volume
13
issue
8
article number
1485
publisher
MDPI AG
external identifiers
  • scopus:85137405055
  • pmid:36011397
ISSN
2073-4425
DOI
10.3390/genes13081485
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2022 by the author.
id
55d82ca3-076d-4f54-95e7-88b981c7d792
date added to LUP
2022-11-23 08:18:21
date last changed
2025-05-16 06:10:42
@article{55d82ca3-076d-4f54-95e7-88b981c7d792,
  abstract     = {{<p>Term synonymous variation is widely used, but frequently in a wrong or misleading meaning and context. Twenty three point eight % of possible nucleotide substitution types in the universal genetic code are for synonymous amino acid changes, but when these variants have a phenotype and functional effect, they are very seldom synonymous. Such variants may manifest changes at DNA, RNA and/or protein levels. Large numbers of variations are erroneously annotated as synonymous, which causes problems e.g., in clinical genetics and diagnosis of diseases. To facilitate precise communication, novel systematics and nomenclature are introduced for variants that when looking only at the genetic code seem like synonymous, but which have phenotypes. A new term, unsense variant is defined as a substitution in the mRNA coding region that affects gene expression and protein production without introducing a stop codon in the variation site. Such variants are common and need to be correctly annotated. Proper naming and annotation are important also to increase awareness of these variants and their consequences.</p>}},
  author       = {{Vihinen, Mauno}},
  issn         = {{2073-4425}},
  keywords     = {{annotation; mutation; synonymous variation; terminology; variation interpretation; variation naming}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{8}},
  publisher    = {{MDPI AG}},
  series       = {{Genes}},
  title        = {{When a Synonymous Variant Is Nonsynonymous}},
  url          = {{http://dx.doi.org/10.3390/genes13081485}},
  doi          = {{10.3390/genes13081485}},
  volume       = {{13}},
  year         = {{2022}},
}