Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBP6_Very_Strong
The ENST00000640807.1(KCNMA1):c.3363-6C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,606,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
KCNMA1 (HGNC:6284): (potassium calcium-activated channel subfamily M alpha 1) This gene encodes the alpha subunit of calcium-activated BK channel. The encoded protein is involved in several physiological processes including smooth muscle contraction, neurotransmitter release and neuronal excitability. Mutations in this gene are associated with a spectrum of neurological disorders including Paroxysmal Nonkinesigenic Dyskinesia 3, Idiopathic Generalized Epilepsy 16 and Liang-Wang syndrome. [provided by RefSeq, Aug 2022]
BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-76877899-G-T is Benign according to our data. Variant chr10-76877899-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2578617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-76877899-G-T is described in Lovd as [Likely_benign].
Likely benign, criteria provided, single submitter
clinical testing
CeGaT Center for Human Genetics Tuebingen
Jul 01, 2023
KCNMA1: BP4, BS2 -
KCNMA1-related disorder Benign:1
Likely benign, criteria provided, single submitter
clinical testing
PreventionGenetics, part of Exact Sciences
Feb 22, 2022
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -