rs201721843
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7
The NM_001161352.2(KCNMA1):c.3507G>A(p.Thr1169=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,613,948 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
KCNMA1
NM_001161352.2 synonymous
NM_001161352.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.365
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 Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
BP6
?
Variant 10-76887470-C-T is Benign according to our data. Variant chr10-76887470-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 444226.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.365 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNMA1 | NM_001161352.2 | c.3507G>A | p.Thr1169= | synonymous_variant | 28/28 | ENST00000286628.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNMA1 | ENST00000286628.14 | c.3507G>A | p.Thr1169= | synonymous_variant | 28/28 | 1 | NM_001161352.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152094Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000722 AC: 18AN: 249220Hom.: 0 AF XY: 0.0000593 AC XY: 8AN XY: 134890
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GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461854Hom.: 0 Cov.: 33 AF XY: 0.0000413 AC XY: 30AN XY: 727220
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GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152094Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74280
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | KCNMA1: BP4, BP7 - |
Generalized epilepsy-paroxysmal dyskinesia syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
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DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at