9-135714735-CG-CGG
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_020822.3(KCNT1):c.254+19dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000222 in 1,348,494 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000067 ( 0 hom., cov: 21)
Exomes 𝑓: 0.0000017 ( 0 hom. )
Consequence
KCNT1
NM_020822.3 intron
NM_020822.3 intron
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.114
Publications
2 publications found
Genes affected
KCNT1 (HGNC:18865): (potassium sodium-activated channel subfamily T member 1) Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a sodium-activated potassium channel subunit which is thought to function in ion conductance and developmental signaling pathways. Mutations in this gene cause the early-onset epileptic disorders, malignant migrating partial seizures of infancy and autosomal dominant nocturnal frontal lobe epilepsy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]
KCNT1 Gene-Disease associations (from GenCC):
- childhood-onset epilepsy syndromeInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- developmental and epileptic encephalopathy, 14Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
- malignant migrating partial seizures of infancyInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
- autosomal dominant nocturnal frontal lobe epilepsy 5Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
- autosomal dominant nocturnal frontal lobe epilepsyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_020822.3. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| KCNT1 | TSL:1 MANE Select | c.254+19dupG | intron | N/A | ENSP00000360822.2 | Q5JUK3-3 | |||
| KCNT1 | TSL:1 | n.254+19dupG | intron | N/A | ENSP00000418777.1 | F8WC49 | |||
| KCNT1 | TSL:5 | c.254+19dupG | intron | N/A | ENSP00000417851.2 | Q5JUK3-2 |
Frequencies
GnomAD3 genomes 0.00000668 AC: 1AN: 149694Hom.: 0 Cov.: 21 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
149694
Hom.:
Cov.:
21
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
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Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
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Gnomad NFE
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Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000212 AC: 2AN: 94148 AF XY: 0.0000184 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
94148
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.00000167 AC: 2AN: 1198800Hom.: 0 Cov.: 30 AF XY: 0.00000170 AC XY: 1AN XY: 589896 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
2
AN:
1198800
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
589896
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:
23618
American (AMR)
AF:
AC:
0
AN:
22324
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
17264
East Asian (EAS)
AF:
AC:
0
AN:
22950
South Asian (SAS)
AF:
AC:
0
AN:
59256
European-Finnish (FIN)
AF:
AC:
0
AN:
35922
Middle Eastern (MID)
AF:
AC:
0
AN:
4250
European-Non Finnish (NFE)
AF:
AC:
1
AN:
967642
Other (OTH)
AF:
AC:
1
AN:
45574
⚠️ 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: 0.225
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000668 AC: 1AN: 149694Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0AN XY: 72988 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
149694
Hom.:
Cov.:
21
AF XY:
AC XY:
0
AN XY:
72988
show subpopulations
African (AFR)
AF:
AC:
1
AN:
40964
American (AMR)
AF:
AC:
0
AN:
15050
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3434
East Asian (EAS)
AF:
AC:
0
AN:
5128
South Asian (SAS)
AF:
AC:
0
AN:
4810
European-Finnish (FIN)
AF:
AC:
0
AN:
9876
Middle Eastern (MID)
AF:
AC:
0
AN:
312
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67164
Other (OTH)
AF:
AC:
0
AN:
2050
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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
Publications
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