rs118192254
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_004519.4(KCNQ3):c.2462A>G(p.Asn821Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,614,168 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). Synonymous variant affecting the same amino acid position (i.e. N821N) has been classified as Likely benign.
Frequency
Consequence
NM_004519.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNQ3 | NM_004519.4 | c.2462A>G | p.Asn821Ser | missense_variant | 15/15 | ENST00000388996.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ3 | ENST00000388996.10 | c.2462A>G | p.Asn821Ser | missense_variant | 15/15 | 1 | NM_004519.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000230 AC: 35AN: 152168Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000219 AC: 55AN: 251326Hom.: 0 AF XY: 0.000199 AC XY: 27AN XY: 135842
GnomAD4 exome AF: 0.000149 AC: 218AN: 1461882Hom.: 0 Cov.: 32 AF XY: 0.000169 AC XY: 123AN XY: 727240
GnomAD4 genome ? AF: 0.000230 AC: 35AN: 152286Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74468
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 06, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 24, 2021 | This variant is associated with the following publications: (PMID: 20437616, 16235065, 18698150, 17765802) - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2023 | KCNQ3: BP4 - |
Benign neonatal seizures Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 30, 2018 | This alteration is classified as 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. - |
Benign Neonatal Epilepsy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Seizures, benign familial neonatal, 2 Other:1
not provided, no classification provided | literature only | GeneReviews | - | Found in a typical family with BFNE who also had a KCNQ2 deletion/insertion (likely pathogenic); the KCNQ3 variant does not cosegregate with the disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at