1-40784203-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_004700.4(KCNQ4):c.110G>A(p.Gly37Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000679 in 147,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G37S) has been classified as Uncertain significance.
Frequency
Consequence
NM_004700.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNQ4 | NM_004700.4 | c.110G>A | p.Gly37Asp | missense_variant | Exon 1 of 14 | ENST00000347132.10 | NP_004691.2 | |
KCNQ4 | NM_172163.3 | c.110G>A | p.Gly37Asp | missense_variant | Exon 1 of 13 | NP_751895.1 | ||
KCNQ4 | XM_047434057.1 | c.110G>A | p.Gly37Asp | missense_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.110G>A | p.Gly37Asp | missense_variant | Exon 1 of 14 | 1 | NM_004700.4 | ENSP00000262916.6 | ||
KCNQ4 | ENST00000509682.6 | c.110G>A | p.Gly37Asp | missense_variant | Exon 1 of 13 | 5 | ENSP00000423756.2 |
Frequencies
GnomAD3 genomes AF: 0.00000679 AC: 1AN: 147254Hom.: 0 Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 980186Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 468466
GnomAD4 genome AF: 0.00000679 AC: 1AN: 147254Hom.: 0 Cov.: 32 AF XY: 0.0000140 AC XY: 1AN XY: 71652
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 37 of the KCNQ4 protein (p.Gly37Asp). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KCNQ4 protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at