rs745970423
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PP2PP3_ModerateBS2
The ENST00000322893.12(KCNH5):c.460C>T(p.Arg154Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000217 in 1,613,290 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R154R) has been classified as Likely benign.
Frequency
Consequence
ENST00000322893.12 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNH5 | NM_139318.5 | c.460C>T | p.Arg154Trp | missense_variant | 5/11 | ENST00000322893.12 | NP_647479.2 | |
KCNH5 | NM_172375.3 | c.460C>T | p.Arg154Trp | missense_variant | 5/10 | NP_758963.1 | ||
KCNH5 | XM_047431275.1 | c.460C>T | p.Arg154Trp | missense_variant | 5/10 | XP_047287231.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNH5 | ENST00000322893.12 | c.460C>T | p.Arg154Trp | missense_variant | 5/11 | 1 | NM_139318.5 | ENSP00000321427 | P1 | |
KCNH5 | ENST00000420622.6 | c.460C>T | p.Arg154Trp | missense_variant | 5/10 | 1 | ENSP00000395439 | |||
KCNH5 | ENST00000394964.3 | n.625C>T | non_coding_transcript_exon_variant | 5/7 | 1 | |||||
KCNH5 | ENST00000394968.2 | c.286C>T | p.Arg96Trp | missense_variant | 5/11 | 2 | ENSP00000378419 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152104Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251096Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135694
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461186Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 726870
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152104Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74302
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 07, 2020 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with KCNH5-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with tryptophan at codon 154 of the KCNH5 protein (p.Arg154Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at