How do you translate from a genomics coordinate to a protein level coordinate or effect. Eg if you have a variant like 3:38550782-38550782:C/A how do you specify its effect on the protein amino acid.

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Translating genomic coordinates to protein effects is a fundamental process in genomics. When we have a variant like chromosome 3 position 38550782 with a C to A change, we need to map this genomic position to determine its effect on the resulting protein. This involves identifying which gene contains this position and how the nucleotide change affects the amino acid sequence. The first step in translating genomic coordinates to protein effects is gene annotation mapping. We start with our genomic position on chromosome 3 at position 38550782. This coordinate is then queried against annotation databases like Ensembl or RefSeq to identify which genes overlap this position. The database returns information about the gene SCN5A, its canonical transcript, and that our variant falls within exon 12 of 28 total exons. The second step involves coordinate transformation. We convert the genomic position 38550782 to transcript coordinates, accounting for introns and UTRs. This gives us position c.1234 in the transcript. We then map to the coding sequence coordinates, which removes the 5-prime UTR. Finally, we identify that this position falls in codon 412, specifically in the second position of the GGC codon, which codes for glycine. In step three, we analyze the codon change and translate it to amino acids. The original codon GGC codes for glycine, while the variant codon GAC codes for aspartic acid. The C to A substitution in the second position of the codon results in a missense mutation, changing the amino acid from glycine to aspartic acid at position 412 of the protein. This represents a significant chemical change from a small, flexible amino acid to a larger, negatively charged one. The final step produces the standard protein nomenclature. Our genomic variant Chr3:38550782:C>A translates to the protein change p.Gly412Asp, meaning glycine at position 412 is changed to aspartic acid. This complete workflow from genomic coordinates to protein effects is automated by bioinformatics tools like Variant Effect Predictor, SnpEff, and ANNOVAR, which handle the complex coordinate transformations and provide standardized HGVS nomenclature for clinical interpretation.