6-73133459-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PM5PP2PP3PP5_Moderate
The NM_019842.4(KCNQ5):c.1286G>T(p.Ser429Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S429R) has been classified as Likely pathogenic.
Frequency
Consequence
NM_019842.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNQ5 | NM_019842.4 | c.1286G>T | p.Ser429Ile | missense_variant | 10/14 | ENST00000370398.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ5 | ENST00000370398.6 | c.1286G>T | p.Ser429Ile | missense_variant | 10/14 | 1 | NM_019842.4 | P4 | |
KCNQ5-AS1 | ENST00000666538.1 | n.577-1076C>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2017 | This sequence change replaces serine with isoleucine at codon 448 of the KCNQ5 protein (p.Ser448Ile). The serine residue is moderately conserved and there is a large physicochemical difference between serine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in an individual affected with epileptic encephalopathy (PMID: 28669405). ClinVar contains an entry for this variant (Variation ID: 431387). Experimental studies have shown that this missense change resulted in slowed activation kinetics with no effect on deactivation or channel expression (PMID: 28669405). For these reasons, this variant has been classified as Pathogenic. - |
Intellectual disability, autosomal dominant 46 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 26, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at