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Analysis of p.Gly576Ala 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 G576A gnomAD (123,136 exomes): 5.07e-03; variant G576A gnomAD (15,496 genomes): 4.78e-03
    variant G576V gnomAD (123,136 exomes): 4.00e-06


  • Ortholog conservation: Help


    Number of sequences AAPI* AAPIR** Number of divergencies Number of mutant A576 Number of gaps Conservation of G576 Conservation - gap
    50 80.72% 91.41% 8
    show divergencies
    0
    details
    0
    details
    84.00% (42 / 50) 84.00% (42 / 50)


    The wild-type residue G576 is highly conserved among the CFTR orthologs: 84% (42 / 50 CFTR orthologs)
    The variant G576A 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 576). 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 NBD1 of CF Transmembrane conductance Regulator has been shown to interact with:


    The residue p.Gly576 belongs to the domain NBD1.

    423
    649


    NBD1: is the nucleotide binding domain 1, also called the ATP-binding cassette (ABC). It contains the Walker A (P-loop) and Walker B motifs, the C-motif (also known as the signature sequence), the A-, D-, Q-, and H-loops.








    NBD1 of CF Transmembrane conductance Regulator domain alignment including p.Gly576 residue.



    Number of sequences AAPID***
    (from aa 423 to aa 649)
    AAPIR! Number of divergencies Number of mutant Number of gaps Conservation of G576 Conservation - gap
    3982 26.61% 39.19% 3382
    show divergencies
    694 2 15.02% (598 / 3982) 15.03% (598 / 3980)



    ***AAPID: Alignment Average Percentage Identity of the Domain (positions are indicated).
    !AAPIR: Alignment Average Percentage Identity of the Region (20 residues surrounding position 576). AAPIR appears in green if it is more than 10% compared to AAPID, in red if less than 10%.

    The wild-type residue G576 belongs to the NBD1 domain and is conserved at 15.02% among the NBD1 homologs (598 / 3982 NBD1 homologs)
    The variant G576A has been found among the NBD1 homologs with a high frequency: 17.43% (694 / 3982 NBD1 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 NBD1 domain conservation:





    Display methods


  • Refer to the Help page for more details.


  • Secondary structure analysis: Help


    Residue p.Gly576 is predicted to belong to a loop. Probability is 0.940.

    Direct environment is as follow:

    DSPFG576YLDV
    CCCCCCCCH


    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 G576A has been been described as Conflicting interpretations of pathogenicity - criteria provided, conflicting interpretations - (ClinVar for more details)


  • Patients data: CFTR-France

  • Variant G576A might correspond to:


    Variant details from CFTR-France:
    Name NM_000492.3:c.1727G>C
    Protein name NP_000483.3:p.(Gly576Ala)
    Genomic name chr7:g.117230454G>C
    Class disease-causing


    Patients carrying this variant in CFTR-France:
    Total number of patients 111
    Aquagenic palmoplantar keratoderma 2
    Asymptomatic compound heterozygote 13
    CF 6
    CFTR-RD81
    • Bronchiectasis  6
    • CBAVD  50
    • CRS-NP  2
    • Other  12
    • Pancreatitis  11
    Fetal bowel anomalies 1
    Pending 5
    Pending (NBS) 2
    Pending non-CF 1

    (CFTR-France for more details)




  • Additional resources:



  • References


    CYSMA has completed its calculations; Execution time: 14 wallclock secs (10.30 usr 0.04 sys + 2.69 cusr 0.06 csys = 13.09 CPU)