rs185511111
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The ENST00000388996.10(KCNQ3):c.1885G>T(p.Val629Phe) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. 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. V629I) has been classified as Likely benign.
Frequency
Consequence
ENST00000388996.10 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNQ3 | NM_004519.4 | c.1885G>T | p.Val629Phe | missense_variant, splice_region_variant | 15/15 | ENST00000388996.10 | NP_004510.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNQ3 | ENST00000388996.10 | c.1885G>T | p.Val629Phe | missense_variant, splice_region_variant | 15/15 | 1 | NM_004519.4 | ENSP00000373648 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152052Hom.: 0 Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152052Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74270
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 28, 2018 | The p.V629F variant (also known as c.1885G>T) is located in coding exon 15 of the KCNQ3 gene. The valine at codon 629 is replaced by phenylalanine, an amino acid with highly similar properties. This change occurs in the first base pair of coding exon 15. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 01, 2013 | p.Val629Phe (GTT>TTT): c.1885 G>T in exon 15 of the KCNQ3 gene. The Val629Phe missense change in the KCNQ3 has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a conservative substitution of one uncharged, non-polar amino acid for another. It alters a highly conserved position in the C-terminal region of the protein. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether Val629Phe is a disease-causing mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at