rs776842795
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate
The NM_139318.5(KCNH5):c.611C>T(p.Pro204Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,750 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P204S) has been classified as Uncertain significance.
Frequency
Consequence
NM_139318.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNH5 | NM_139318.5 | c.611C>T | p.Pro204Leu | missense_variant | 6/11 | ENST00000322893.12 | |
KCNH5 | NM_172375.3 | c.611C>T | p.Pro204Leu | missense_variant | 6/10 | ||
KCNH5 | XM_047431275.1 | c.611C>T | p.Pro204Leu | missense_variant | 6/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNH5 | ENST00000322893.12 | c.611C>T | p.Pro204Leu | missense_variant | 6/11 | 1 | NM_139318.5 | P1 | |
KCNH5 | ENST00000420622.6 | c.611C>T | p.Pro204Leu | missense_variant | 6/10 | 1 | |||
KCNH5 | ENST00000394964.3 | n.776C>T | non_coding_transcript_exon_variant | 6/7 | 1 | ||||
KCNH5 | ENST00000394968.2 | c.437C>T | p.Pro146Leu | missense_variant | 6/11 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250672Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135472
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461750Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727178
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 28, 2021 | 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 present in population databases (rs776842795, ExAC 0.009%). This sequence change replaces proline with leucine at codon 204 of the KCNH5 protein (p.Pro204Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at