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Table 2 GALNS nucleotide sequence variants with potential significance in the generation of the GALNS aberrant splicing products detected in Pt2 and Pt3

From: Mis-splicing of the GALNS gene resulting from deep intronic mutations as a cause of Morquio a disease

Chr: Pos (GRCh37.p13) Zygosity Parental Zygosity Variant Type Identifier (dbSNP 149, NCBI) Exon/Intron MAF HSF Summary/CADD score
Pt2
16:88898099 Heterozygous Paternal (heterozygous) c.1002 + 307G > C rs866140272 INTRON 9 ESE gain and alterations to various ESRs - CADD 3.002
Pt3
16:88901744 Heterozygous Paternal (heterozygous) c.775C > A; p.Arg259Arg rs61742258 EXON 8 0.002 Cryptic donor splice site created, ESE loss and ESS gain - CADD 14.49
16:88901827 Heterozygous Maternal (heterozygous) c.759-67G > A rs565875595 INTRON 7 0.001 ESE gain and ESS loss - CADD 6.652
16:88902194 Heterozygous Paternal (heterozygous) c.697G > A; p.Asp233Asn rs753051547 EXON 7 Alteration of an exonic ESE site - CADD 24.1
16:88905035 Heterozygous Maternal (heterozygous) c.423-862C > T INTRON 4 Cryptic donor splice site created - CADD 0.094
  1. - = not present in gnomAD browser beta (http://gnomad.broadinstitute.org/); MAF = minor allele frequency; ESE = exonic splicing enhancer; ESS = exonic splicing silencer; ESRs = exonic splicing regulatory sequences; HSF (Human Splicing Finder) predictions = a tool which assesses the potential impact of these variants on the mRNA splicing phenotype (http://www.umd.be/HSF3/); CADD = Combined Annotation Dependent Depletion = a tool for scoring the deleteriousness of single nucleotide variants as well as insertion/deletion variants in the human genome. A CADD score of > 10 is applied as a threshold to identify high-confidence disease-causing mutations [27]