1-40784129-T-TCCCCCGCCCGGGGACGC
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_004700.4(KCNQ4):c.44_60dupCCGGGGACGCCCCCCGC(p.Ala21ProfsTer9) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_004700.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNQ4 | NM_004700.4 | c.44_60dupCCGGGGACGCCCCCCGC | p.Ala21ProfsTer9 | frameshift_variant | Exon 1 of 14 | ENST00000347132.10 | NP_004691.2 | |
KCNQ4 | NM_172163.3 | c.44_60dupCCGGGGACGCCCCCCGC | p.Ala21ProfsTer9 | frameshift_variant | Exon 1 of 13 | NP_751895.1 | ||
KCNQ4 | XM_047434057.1 | c.44_60dupCCGGGGACGCCCCCCGC | p.Ala21ProfsTer9 | frameshift_variant | Exon 1 of 13 | XP_047290013.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNQ4 | ENST00000347132.10 | c.44_60dupCCGGGGACGCCCCCCGC | p.Ala21ProfsTer9 | frameshift_variant | Exon 1 of 14 | 1 | NM_004700.4 | ENSP00000262916.6 | ||
KCNQ4 | ENST00000509682.6 | c.44_60dupCCGGGGACGCCCCCCGC | p.Ala21ProfsTer9 | frameshift_variant | Exon 1 of 13 | 5 | ENSP00000423756.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 11
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
This sequence change creates a premature translational stop signal (p.Ala21Profs*9) in the KCNQ4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KCNQ4 are known to be pathogenic (PMID: 23717403). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with KCNQ4-related conditions. For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at