GeneBe

rs55843930

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_020822.3(KCNT1):​c.2944-46_2944-7delCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000102 in 393,614 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

KCNT1
NM_020822.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.81

Publications

0 publications found
Variant links:
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 syndrome
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • developmental and epileptic encephalopathy, 14
    Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
  • malignant migrating partial seizures of infancy
    Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
  • autosomal dominant nocturnal frontal lobe epilepsy 5
    Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • autosomal dominant nocturnal frontal lobe epilepsy
    Inheritance: 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 0 ACMG points.

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.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
KCNT1
NM_020822.3
MANE Select
c.2944-46_2944-7delCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCT
splice_region intron
N/ANP_065873.2
KCNT1
NM_001272003.2
c.2809-46_2809-7delCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCT
splice_region intron
N/ANP_001258932.1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
KCNT1
ENST00000371757.7
TSL:1 MANE Select
c.2944-46_2944-7delCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCT
splice_region intron
N/AENSP00000360822.2
KCNT1
ENST00000460750.5
TSL:1
n.*2554-46_*2554-7delCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCT
splice_region intron
N/AENSP00000418777.1
KCNT1
ENST00000487664.5
TSL:5
c.2944-46_2944-7delCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCT
splice_region intron
N/AENSP00000417851.2

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
AF:
0.0000102
AC:
4
AN:
393614
Hom.:
0
AF XY:
0.00000956
AC XY:
2
AN XY:
209124
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
11432
American (AMR)
AF:
0.00
AC:
0
AN:
23274
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
14030
East Asian (EAS)
AF:
0.00
AC:
0
AN:
23340
South Asian (SAS)
AF:
0.00
AC:
0
AN:
46194
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
29860
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
1740
European-Non Finnish (NFE)
AF:
0.0000180
AC:
4
AN:
221760
Other (OTH)
AF:
0.00
AC:
0
AN:
21984
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000130562), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.263
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.8
Mutation Taster
=100/0
polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs55843930; hg19: chr9-138676328; API