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Analysis of p.Ala959Val variant, CFTR gene, CF Transmembrane conductance Regulator protein (1480 residues)


Data provided and calculated by CYSMA must be considered as predictions.
They are meant for educational purposes only and are provided with NO WARRANTY with respect to their biological reliability.



  • Allele frequency:

    variant A959T gnomAD (123,136 exomes): 3.98e-06
    variant A959V gnomAD (123,136 exomes): 7.96e-06


  • Ortholog conservation: Help


    Number of sequences AAPI* AAPIR** Number of divergencies Number of mutant V959 Number of gaps Conservation of A959 Conservation - gap
    50 80.72% 83.36% 2
    show divergencies
    0
    details
    0
    details
    96.00% (48 / 50) 96.00% (48 / 50)


    The wild-type residue A959 is highly conserved among the CFTR orthologs: 96% (48 / 50 CFTR orthologs)
    The variant A959V has never been found among the CFTR orthologs

    *AAPI: Alignment Average Percentage Identity
    **AAPIR: Alignment Average Percentage Identity of the Region (20 residues surrounding position 959). AAPIR appears in green if it is more than 10% compared to AAPI, in red if less than 10%.
    Click here for more details on the alignment.


    CYSMA's visualizing modules for Ortholog conservation:





    ⬇ Download the region alignment (50 residues, Fasta format)
    ⬇ Download the CFTR phylogenic tree



    Display methods


  • Domain conservation: Help

    The domain MSD2 of CF Transmembrane conductance Regulator has been shown to interact with:


    The residue p.Ala959 belongs to the domain MSD2.

    844
    1203


    MSD2: is the membrane-spanning domain 2, composed of six transmembrane helices (TM7-TM12).
    Four of the six TMs protrude into the cytosol to form the intracellular loops. ICL3 (between TM8 and TM9) and ICL4 (between TM10 and TM11). ICL3 contacts the NBD2 at the level of the ATP-binding site, while ICL4 binds in a groove located at the surface of NBD1.








    MSD2 of CF Transmembrane conductance Regulator domain alignment including p.Ala959 residue.



    Number of sequences AAPID***
    (from aa 844 to aa 1203)
    AAPIR! Number of divergencies Number of mutant Number of gaps Conservation of A959 Conservation - gap
    127 34.22% 42.27% 36
    show divergencies
    0 0 71.65% (91 / 127) 71.65% (91 / 127)



    ***AAPID: Alignment Average Percentage Identity of the Domain (positions are indicated).
    !AAPIR: Alignment Average Percentage Identity of the Region (20 residues surrounding position 959). AAPIR appears in green if it is more than 10% compared to AAPID, in red if less than 10%.

    The wild-type residue A959 belongs to the MSD2 domain and is conserved at 71.65% among the MSD2 homologs (91 / 127 MSD2 homologs)
    The variant A959V has never been found among the MSD2 homologs

    Divergencies show the amino acids which have been selected in the evolution. Residues present in more than 10% of the sequences are highlighted in blue.
    Please note that CYSMA does not consider splicing alterations.
    Refer to the Help page for more details.



    CYSMA's visualizing modules for MSD2 domain conservation:





    Display methods


  • Refer to the Help page for more details.


  • Secondary structure analysis: Help


    Residue p.Ala959 is predicted to belong to a loop. Probability is 0.593.

    Direct environment is as follow:

    SVLQA959PMST
    HHHHCCCCC


    Display methods











  • 3D analysis: Help


    Models provided and analysed by CYSMA must be considered as predictions, therefore be careful when interpreting the results. All efforts have been made to build structures of quality, however, they are provided with NO WARRANTY as to their accuracy with the real biological molecules studied.

    Wild type and predicted mutant structures have been compared. You will find the results below.


  • Clinical significance:

    The variant A959V has been been described as Uncertain significance - criteria provided, single submitter - (ClinVar for more details)


  • Patients data: CFTR-France

  • Variant A959V might correspond to:


    Variant details from CFTR-France:
    Name NM_000492.3:c.2876C>T
    Protein name NP_000483.3:p.(Ala959Val)
    Genomic name chr7:g.117243804C>T
    Class unclassified

    No patient found

    (CFTR-France for more details)




  • Additional resources:



  • References


    CYSMA has completed its calculations; Execution time: 16 wallclock secs (11.50 usr 0.04 sys + 3.93 cusr 0.05 csys = 15.52 CPU)