NM_004700.4:c.110dupG
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_004700.4(KCNQ4):c.110dupG(p.Gly38ArgfsTer198) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 147,406 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_004700.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNQ4 | NM_004700.4 | c.110dupG | p.Gly38ArgfsTer198 | frameshift_variant | Exon 1 of 14 | ENST00000347132.10 | NP_004691.2 | |
KCNQ4 | NM_172163.3 | c.110dupG | p.Gly38ArgfsTer198 | frameshift_variant | Exon 1 of 13 | NP_751895.1 | ||
KCNQ4 | XM_047434057.1 | c.110dupG | p.Gly38ArgfsTer198 | 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.110dupG | p.Gly38ArgfsTer198 | frameshift_variant | Exon 1 of 14 | 1 | NM_004700.4 | ENSP00000262916.6 | ||
KCNQ4 | ENST00000509682.6 | c.110dupG | p.Gly38ArgfsTer198 | frameshift_variant | Exon 1 of 13 | 5 | ENSP00000423756.2 |
Frequencies
GnomAD3 genomes AF: 0.0000136 AC: 2AN: 147406Hom.: 0 Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000185 AC: 18AN: 971506Hom.: 0 Cov.: 24 AF XY: 0.0000151 AC XY: 7AN XY: 464262
GnomAD4 genome AF: 0.0000136 AC: 2AN: 147406Hom.: 0 Cov.: 32 AF XY: 0.0000139 AC XY: 1AN XY: 71708
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:1
This sequence change creates a premature translational stop signal (p.Gly38Argfs*198) 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. -
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is not a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at