rs199682667
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_004519.4(KCNQ3):āc.2614A>Gā(p.Ile872Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000931 in 1,611,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004519.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNQ3 | NM_004519.4 | c.2614A>G | p.Ile872Val | missense_variant | 15/15 | ENST00000388996.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ3 | ENST00000388996.10 | c.2614A>G | p.Ile872Val | missense_variant | 15/15 | 1 | NM_004519.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000361 AC: 9AN: 249476Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135060
GnomAD4 exome AF: 0.0000960 AC: 140AN: 1459028Hom.: 0 Cov.: 32 AF XY: 0.000106 AC XY: 77AN XY: 725970
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74368
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 21, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2023 | - - |
Benign neonatal seizures Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 18, 2023 | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 872 of the KCNQ3 protein (p.Ile872Val). This variant is present in population databases (rs199682667, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with KCNQ3-related conditions. ClinVar contains an entry for this variant (Variation ID: 205995). 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 not expected to disrupt KCNQ3 protein function with a negative predictive value of 95%. 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. - |
Seizures, benign familial neonatal, 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 24, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at