Title :

Performance of meta-predictors for the classification of MED13L missense variations, implication of raw parameters.

Author(s) :

Smol, Thomas [Auteur]
Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 [RADEME]
Frenois, Frederic [Auteur]
Maladies Rares du Développement : Génétique, Régulation et Protéomique (RADEME) - ULR 7364
Manouvrier, Sylvie [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 [RADEME]
Petit, Florence [Auteur]
Maladies Rares du Développement : Génétique, Régulation et Protéomique (RADEME) - ULR 7364
Ghoumid, Jamal [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 [RADEME]

Journal title :

European Journal of Medical Genetics

Abbreviated title :

Eur J Med Genet

Volume number :

65

Pages :

104398

Publication date :

2021-11-24

ISSN :

1878-0849

English keyword(s) :

MED13L
Missense
Conservation
In-silico algorithm
Variant interpretation

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

MED13L syndrome is a rare congenital disorder comprising moderate intellectual disability, hypotonia and facial dysmorphism. Whole exome or genome sequencing in patients with non-specific neurodevelopmental disorders leads ...
Show more >MED13L syndrome is a rare congenital disorder comprising moderate intellectual disability, hypotonia and facial dysmorphism. Whole exome or genome sequencing in patients with non-specific neurodevelopmental disorders leads to identification of an increasing number of MED13L missense variations of unknown signification. The aim of our study was to identify relevant annotation parameters enhancing discrimination between candidate pathogenic or neutral missense variations, and to assess the performance of seven meta-predictor algorithms: BayesDel, CADD, DANN, FATHMM-XF, M-CAP, MISTIC and REVEL for the classification of MED13L missense variants. Significant differences were identified for five parameters: global conservation through verPhyloP and verPhCons scores; physico-chemical difference between amino acids estimated by Grantham scores; conservation of residues between MED13L and MED13 protein; proximity to phosphorylation sites for pathogenic variations. Among the seven selected in-silico tools, BayesDel, REVEL, and MISTIC provided the most interesting performances to discriminate pathogenic from neutral missense variations. Individual gene parameter studies with MED13L have provided expertise on elements of annotation improving meta-predictor choices. The in-silico approach allows us to make valuable hypotheses to predict the involvement of these amino acids in MED13L pathogenic missense variations.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CHU Lille

Collections :

• Maladies Rares du Développement : Génétique, Régulation et Protéomique (RADEME) - ULR 7364

Submission date :

2023-06-05T07:12:15Z
2024-02-21T12:50:02Z