12-5044182-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002234.4(KCNA5):c.35G>A(p.Gly12Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,384,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G12G) has been classified as Likely benign.
Frequency
Consequence
NM_002234.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNA5 | NM_002234.4 | c.35G>A | p.Gly12Asp | missense_variant | 1/1 | ENST00000252321.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNA5 | ENST00000252321.5 | c.35G>A | p.Gly12Asp | missense_variant | 1/1 | NM_002234.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000746 AC: 1AN: 134006Hom.: 0 AF XY: 0.0000137 AC XY: 1AN XY: 73198
GnomAD4 exome AF: 0.00000144 AC: 2AN: 1384736Hom.: 0 Cov.: 31 AF XY: 0.00000146 AC XY: 1AN XY: 683458
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Atrial fibrillation, familial, 7 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 05, 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with KCNA5-related conditions. While this variant is present in population databases (rs774385439), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces glycine with aspartic acid at codon 12 of the KCNA5 protein (p.Gly12Asp). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at