Table 1.
KCNQ4 variants in the current study and pathogenicity prediction analysis.
| Family | Genomic position (GRCh37/hg19) | HGVS | Zygosity | Inheritance | In silico Prediction | Ethnicity MAF | Global MAF | ACMG/AMP 2018 guidelines | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Nucleotide change | Amino Acid change | CADD | REVEL | GERP | KRGDB (1722 individuals) | ExAC | gnomAD | Criteria | Classification | ||||
| SB228-442 | Chr1:41285116-41285118 | c.806_808del | p.Ser269del (p.S269del) | Het | Dominant | 19.1 | NA | 5.08 | Absent | Absent | Absent | PM1, PM2, PM4 PS3_supporting | Likely pathogenic |
| SB155-271 | Chr1:41285121-41285126 | c.811_816del |
p.Ala271_ Asp272del (p.A271_ D272del) |
Het | De novo* | 22.7 | NA | 5.08 | Absent | Absent | Absent | PS2_moderate, PM1, PM2, PM4, PS3_supporting | Likely pathogenic |
| SB356-697 | Chr1:41285847 | c.956 G > A |
p.Gly319Asp (p.G319D) |
Het | Dominant | 29.7 | 0.938 | 5.27 | Absent | Absent | Absent | PM2, PP3, PS3_supporting | VUS |
| SB62-110 | Chr1:41285883 | c.992 G > A |
p.Arg331Gln (p.R331Q) |
Het | Dominant | 33 | 0.919 | 5.44 | Absent | Absent | 0.000004102/1 | PM2 PP3, PS3_supporting | VUS |
MAF minor allele frequency, Het heterozygote, VUS variant uncertain significance, NA not available.
Refseq transcript accession number NM_001174069.1; Refseq protein accession number NP_001167540.
HGVS: Human Genome Variation Society (https://www.hgvs.org/).
Sequence Variant Nomenclature (http://varnomen.hgvs.org/).
CADD: Combined Annotation Dependent Depletion (https://cadd.gs.washington.edu/).
REVEL: Rare Exome Variant Ensemble Learner (https://sites.google.com/site/revelgenomics/).
KRGDB: Korean Reference Genome Database (http://coda.nih.go.kr/coda/KRGDB/index.jsp).
ExAC: Exome Aggregation Consortium databases.
gnomAD: The Genome Aggregation Database (https://gnomad.broadinstitute.org/).
ACMG/AMP 2018 guideline (http://wintervar.wglab.org/).
*Note that the biological parents of SB155 were not phenotypically affected or carriers of the variant, as confirmed by haplotype phasing from trio exome sequencing data.