rs2227913
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_001161352.2(KCNMA1):c.3144C>T(p.Ser1048=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000868 in 1,613,570 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000088 ( 1 hom. )
Consequence
KCNMA1
NM_001161352.2 synonymous
NM_001161352.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.368
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant 10-76909969-G-A is Benign according to our data. Variant chr10-76909969-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 464296.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-76909969-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.368 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNMA1 | NM_001161352.2 | c.3144C>T | p.Ser1048= | synonymous_variant | 25/28 | ENST00000286628.14 | NP_001154824.1 | |
KCNMA1-AS1 | NR_120655.1 | n.457+7947G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNMA1 | ENST00000286628.14 | c.3144C>T | p.Ser1048= | synonymous_variant | 25/28 | 1 | NM_001161352.2 | ENSP00000286628 | A2 | |
KCNMA1-AS1 | ENST00000458661.6 | n.425+7947G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152112Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
12
AN:
152112
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000132 AC: 33AN: 250662Hom.: 0 AF XY: 0.000148 AC XY: 20AN XY: 135488
GnomAD3 exomes
AF:
AC:
33
AN:
250662
Hom.:
AF XY:
AC XY:
20
AN XY:
135488
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000876 AC: 128AN: 1461340Hom.: 1 Cov.: 31 AF XY: 0.0000757 AC XY: 55AN XY: 726984
GnomAD4 exome
AF:
AC:
128
AN:
1461340
Hom.:
Cov.:
31
AF XY:
AC XY:
55
AN XY:
726984
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000788 AC: 12AN: 152230Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74412
GnomAD4 genome
AF:
AC:
12
AN:
152230
Hom.:
Cov.:
33
AF XY:
AC XY:
3
AN XY:
74412
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | KCNMA1: BP4, BP7 - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 26, 2018 | - - |
Generalized epilepsy-paroxysmal dyskinesia syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 22, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at