VCV000129358.47 - ClinVar

NM_020822.3(KCNT1):c.2543A>G (p.Glu848Gly)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(15)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_020822.3(KCNT1):c.2543A>G (p.Glu848Gly)

Variation ID: 129358 Accession: VCV000129358.47

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 9q34.3 9: 135778444 (GRCh38) [ NCBI UCSC ] 9: 138670290 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Oct 5, 2015	Dec 22, 2024	Nov 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_020822.3:c.2543A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_065873.2:p.Glu848Gly	missense
NM_001272003.2:c.2408A>G	NP_001258932.1:p.Glu803Gly	missense
NC_000009.12:g.135778444A>G
NC_000009.11:g.138670290A>G
NG_033070.1:g.81260A>G

... more HGVS ... less HGVS

Protein change

E848G, E803G

Other names

Canonical SPDI

NC_000009.12:135778443:A:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00120 (G)

Allele frequency Help The frequency of the allele represented by this VCV record.

1000 Genomes Project 30x 0.00109

1000 Genomes Project 0.00120

Exome Aggregation Consortium (ExAC) 0.00158

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00223

The Genome Aggregation Database (gnomAD), exomes 0.00229

The Genome Aggregation Database (gnomAD) 0.00233

Trans-Omics for Precision Medicine (TOPMed) 0.00235

Links

ClinGen: CA201902 dbSNP: rs149804567 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
KCNT1		-	-	GRCh38 GRCh37	2248	2327

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Autosomal dominant nocturnal frontal lobe epilepsy 5 Developmental and epileptic encephalopathy, 14	Likely benign (1)	criteria provided, single submitter	Jan 29, 2024	RCV001084423.16
not provided	Benign/Likely benign (6)	criteria provided, multiple submitters, no conflicts	Nov 1, 2024	RCV000427452.32
Developmental and epileptic encephalopathy, 14	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	Mar 15, 2022	RCV000988291.10
Autosomal dominant nocturnal frontal lobe epilepsy 5	Benign (1)	criteria provided, single submitter	Mar 15, 2022	RCV002269830.8
Inborn genetic diseases	Likely benign (1)	criteria provided, single submitter	Feb 20, 2019	RCV002312161.9
not specified	Likely benign (4)	criteria provided, multiple submitters, no conflicts	Feb 20, 2015	RCV000176324.26

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely benign (Dec 15, 2014)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Genetic Services Laboratory, University of Chicago Accession: SCV000151547.2 First in ClinVar: May 17, 2014 Last updated: Oct 05, 2015
Likely benign (Feb 20, 2015)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000227958.5 First in ClinVar: Jun 28, 2015 Last updated: Apr 09, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=KCNT1 Number of individuals with the variant: 10 Zygosity: Single Heterozygote Sex: mixed
Likely benign (May 28, 2019)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Developmental and epileptic encephalopathy, 14 Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV001137957.1 First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020
Benign (May 15, 2019)	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Athena Diagnostics Accession: SCV001144342.1 First in ClinVar: Jan 19, 2020 Last updated: Jan 19, 2020	Publications: PubMed (1) PubMed: 26786403
Likely benign (Jun 27, 2022)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000523049.4 First in ClinVar: Mar 08, 2017 Last updated: Mar 04, 2023	Comment: See Variant Classification Assertion Criteria.
Likely benign (Feb 20, 2019)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Inborn genetic diseases Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000846364.4 First in ClinVar: Nov 08, 2018 Last updated: May 01, 2024	Comment: 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 … (more) 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. (less)
Likely benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000313667.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Likely Benign (Nov 07, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: not provided Allele origin: germline	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics Accession: SCV000511254.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Comment: Converted during submission to Likely benign.
Benign (Mar 15, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Developmental and epileptic encephalopathy, 14 Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV002555499.1 First in ClinVar: Jul 30, 2022 Last updated: Jul 30, 2022
Benign (Mar 15, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal dominant nocturnal frontal lobe epilepsy 5 Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV002555500.1 First in ClinVar: Jul 30, 2022 Last updated: Jul 30, 2022
Likely benign (Jan 29, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Autosomal dominant nocturnal frontal lobe epilepsy 5 Developmental and epileptic encephalopathy, 14 Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000563636.9 First in ClinVar: Apr 17, 2017 Last updated: Feb 28, 2024
Likely benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005228597.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Likely benign (Nov 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV002546125.17 First in ClinVar: Jul 09, 2022 Last updated: Dec 22, 2024	Comment: KCNT1: BS1 Number of individuals with the variant: 10
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001954776.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001930537.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021
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Comment:

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.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Nocturnal frontal lobe epilepsy caused by a mutation in the GATOR1 complex gene NPRL3.	Korenke GC	Epilepsia	2016	PMID: 26786403
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=KCNT1	-	-	-	-

Text-mined citations for rs149804567 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Dec 22, 2024

ClinVar Genomic variation as it relates to human health

NM_020822.3(KCNT1):c.2543A>G (p.Glu848Gly)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs149804567 ...