NM_001161352.2:c.460G>A
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001161352.2(KCNMA1):c.460G>A(p.Ala154Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,614,008 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A154S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001161352.2 missense
Scores
Clinical Significance
Conservation
Publications
- generalized epilepsy-paroxysmal dyskinesia syndromeInheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Illumina, G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
- Liang-Wang syndromeInheritance: AD Classification: STRONG Submitted by: Ambry Genetics
- cerebellar atrophy, developmental delay, and seizuresInheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
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ACMG classification
Our verdict: Likely_benign. The variant received -2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152214Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.00000398 AC: 1AN: 251376 AF XY: 0.00 show subpopulations
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461794Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727210 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74356 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Generalized epilepsy-paroxysmal dyskinesia syndrome Uncertain:1
This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 154 of the KCNMA1 protein (p.Ala154Thr). This variant is present in population databases (rs142858967, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with KCNMA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 569859). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt KCNMA1 protein function with a negative predictive value of 80%. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at