10-77637586-TCCGCCGCCGCCGCCG-TCCGCCGCCGCCGCCGCCG
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS1
The NM_001161352.2(KCNMA1):c.56_57insCGG(p.Gly19dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.000563 in 1,524,852 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00087 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00053 ( 0 hom. )
Consequence
KCNMA1
NM_001161352.2 inframe_insertion
NM_001161352.2 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.59
Genes affected
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP6
?
Variant 10-77637586-T-TCCG is Benign according to our data. Variant chr10-77637586-T-TCCG is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 193225.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=4, Uncertain_significance=3, not_provided=1}.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000873 (132/151214) while in subpopulation AMR AF= 0.00203 (31/15238). AF 95% confidence interval is 0.00147. There are 1 homozygotes in gnomad4. There are 51 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNMA1 | NM_001161352.2 | c.56_57insCGG | p.Gly19dup | inframe_insertion | 1/28 | ENST00000286628.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNMA1 | ENST00000286628.14 | c.56_57insCGG | p.Gly19dup | inframe_insertion | 1/28 | 1 | NM_001161352.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000867 AC: 131AN: 151110Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000655 AC: 75AN: 114424Hom.: 0 AF XY: 0.000604 AC XY: 38AN XY: 62920
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:4Other:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 28, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 05, 2016 | - - |
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 13, 2023 | In-frame duplication of 1 amino acid in a repetitive region with no known function; Has not been previously published as pathogenic or benign to our knowledge - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2023 | KCNMA1: BP3, BS2 - |
Generalized epilepsy-paroxysmal dyskinesia syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | This variant, c.54_56dup, results in the insertion of 1 amino acid(s) of the KCNMA1 protein (p.Gly20dup), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 193225). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 31, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
KCNMA1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 08, 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). - |
Infantile epileptic dyskinetic encephalopathy;C5574945:Generalized epilepsy-paroxysmal dyskinesia syndrome Other:1
not provided, no classification provided | phenotyping only | GenomeConnect - Invitae Patient Insights Network | - | Variant interpreted as Uncertain significance and reported on 09-24-2018 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at