rs147165522
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_020822.3(KCNT1):c.985C>T(p.Leu329=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000144 in 1,613,202 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 0.00082 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000073 ( 0 hom. )
Consequence
KCNT1
NM_020822.3 synonymous
NM_020822.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 5.90
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
Variant 9-135759809-C-T is Benign according to our data. Variant chr9-135759809-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 241306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-135759809-C-T is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00082 (125/152372) while in subpopulation AFR AF= 0.00289 (120/41590). AF 95% confidence interval is 0.00247. There are 0 homozygotes in gnomad4. There are 60 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High AC in GnomAd at 125 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNT1 | NM_020822.3 | c.985C>T | p.Leu329= | synonymous_variant | 11/31 | ENST00000371757.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNT1 | ENST00000371757.7 | c.985C>T | p.Leu329= | synonymous_variant | 11/31 | 1 | NM_020822.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000821 AC: 125AN: 152254Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000228 AC: 57AN: 250048Hom.: 0 AF XY: 0.000185 AC XY: 25AN XY: 135410
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GnomAD4 exome AF: 0.0000732 AC: 107AN: 1460830Hom.: 0 Cov.: 32 AF XY: 0.0000523 AC XY: 38AN XY: 726718
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GnomAD4 genome ? AF: 0.000820 AC: 125AN: 152372Hom.: 0 Cov.: 33 AF XY: 0.000805 AC XY: 60AN XY: 74516
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 21, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 02, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Developmental and epileptic encephalopathy, 14;C3554306:Autosomal dominant nocturnal frontal lobe epilepsy 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 21, 2016 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
KCNT1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 11, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Developmental and epileptic encephalopathy, 14 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Autosomal dominant nocturnal frontal lobe epilepsy 5 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at