14-62707539-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3
The NM_139318.5(KCNH5):c.2936C>T(p.Pro979Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000229 in 1,312,026 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. P979S) 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 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNH5 | NM_139318.5 | c.2936C>T | p.Pro979Leu | missense_variant | 11/11 | ENST00000322893.12 | |
KCNH5 | NM_172375.3 | c.*903C>T | 3_prime_UTR_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNH5 | ENST00000322893.12 | c.2936C>T | p.Pro979Leu | missense_variant | 11/11 | 1 | NM_139318.5 | P1 | |
KCNH5 | ENST00000420622.6 | downstream_gene_variant | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000117 AC: 2AN: 170766Hom.: 0 AF XY: 0.0000111 AC XY: 1AN XY: 90132
GnomAD4 exome AF: 0.00000229 AC: 3AN: 1312026Hom.: 0 Cov.: 28 AF XY: 0.00000314 AC XY: 2AN XY: 637322
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 26, 2022 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with KCNH5-related conditions. This variant is present in population databases (rs767274540, gnomAD 0.01%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 979 of the KCNH5 protein (p.Pro979Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at