rs751901610
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3
The NM_001161352.2(KCNMA1):c.147_155delTTCTTCTTC(p.Ser50_Ser52del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,834 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
KCNMA1
NM_001161352.2 disruptive_inframe_deletion
NM_001161352.2 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.22
Publications
3 publications found
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]
KCNMA1 Gene-Disease associations (from GenCC):
- generalized epilepsy-paroxysmal dyskinesia syndromeInheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet, Illumina
- Liang-Wang syndromeInheritance: AD Classification: STRONG Submitted by: Ambry Genetics
- cerebellar atrophy, developmental delay, and seizuresInheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP3
Nonframeshift variant in repetitive region in NM_001161352.2
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001161352.2. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| KCNMA1 | NM_001161352.2 | MANE Select | c.147_155delTTCTTCTTC | p.Ser50_Ser52del | disruptive_inframe_deletion | Exon 1 of 28 | NP_001154824.1 | Q12791-1 | |
| KCNMA1 | NM_001437422.1 | c.147_155delTTCTTCTTC | p.Ser50_Ser52del | disruptive_inframe_deletion | Exon 1 of 28 | NP_001424351.1 | |||
| KCNMA1 | NM_001161353.2 | c.147_155delTTCTTCTTC | p.Ser50_Ser52del | disruptive_inframe_deletion | Exon 1 of 28 | NP_001154825.1 | Q12791-2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| KCNMA1 | ENST00000286628.14 | TSL:1 MANE Select | c.147_155delTTCTTCTTC | p.Ser50_Ser52del | disruptive_inframe_deletion | Exon 1 of 28 | ENSP00000286628.8 | Q12791-1 | |
| KCNMA1 | ENST00000626620.3 | TSL:1 | c.147_155delTTCTTCTTC | p.Ser50_Ser52del | disruptive_inframe_deletion | Exon 1 of 28 | ENSP00000485867.1 | Q12791-2 | |
| KCNMA1 | ENST00000639406.1 | TSL:1 | c.147_155delTTCTTCTTC | p.Ser50_Ser52del | disruptive_inframe_deletion | Exon 1 of 29 | ENSP00000491732.1 | B7ZMF5 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.90e-7 AC: 1AN: 1448834Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 720058 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1448834
Hom.:
AF XY:
AC XY:
0
AN XY:
720058
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33216
American (AMR)
AF:
AC:
0
AN:
43644
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25890
East Asian (EAS)
AF:
AC:
0
AN:
39344
South Asian (SAS)
AF:
AC:
0
AN:
84676
European-Finnish (FIN)
AF:
AC:
0
AN:
52452
Middle Eastern (MID)
AF:
AC:
0
AN:
5750
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1103936
Other (OTH)
AF:
AC:
0
AN:
59926
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
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0
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1
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2
0.00
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
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10
<30
30-35
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Generalized epilepsy-paroxysmal dyskinesia syndrome (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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