rs58604946

Positions:

chr9-135765207-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020822.3(KCNT1):c.1200+12T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,603,724 control chromosomes in the GnomAD database, including 44,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4132 hom., cov: 32)

Exomes 𝑓: 0.23 ( 39972 hom. )

Consequence

KCNT1
NM_020822.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.95

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 9-135765207-T-G is Benign according to our data. Variant chr9-135765207-T-G is described in ClinVar as [Benign]. Clinvar id is 261361.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-135765207-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNT1	NM_020822.3 link	c.1200+12T>G		intron_variant		ENST00000371757.7	NP_065873.2	Q5JUK3-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNT1	ENST00000371757.7 link	c.1200+12T>G		intron_variant		1	NM_020822.3	ENSP00000360822.2		Q5JUK3-3

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34814

AN:

151764

Hom.:

4129

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.289

Gnomad AMR

AF:

0.253

Gnomad ASJ

AF:

0.289

Gnomad EAS

AF:

0.0398

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.330

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.244

GnomAD3 exomes

AF:

0.216

AC:

53898

AN:

250026

Hom.:

6423

AF XY:

0.214

AC XY:

28986

AN XY:

135350

show subpopulations

Gnomad AFR exome

AF:

0.245

Gnomad AMR exome

AF:

0.258

Gnomad ASJ exome

AF:

0.278

Gnomad EAS exome

AF:

0.0401

Gnomad SAS exome

AF:

0.169

Gnomad FIN exome

AF:

0.162

Gnomad NFE exome

AF:

0.242

Gnomad OTH exome

AF:

0.250

GnomAD4 exome

AF:

0.230

AC:

333576

AN:

1451842

Hom.:

39972

Cov.:

AF XY:

0.228

AC XY:

164498

AN XY:

720344

show subpopulations

Gnomad4 AFR exome

AF:

0.249

Gnomad4 AMR exome

AF:

0.258

Gnomad4 ASJ exome

AF:

0.279

Gnomad4 EAS exome

AF:

0.0331

Gnomad4 SAS exome

AF:

0.170

Gnomad4 FIN exome

AF:

0.167

Gnomad4 NFE exome

AF:

0.241

Gnomad4 OTH exome

AF:

0.231

GnomAD4 genome

AF:

0.229

AC:

34837

AN:

151882

Hom.:

4132

Cov.:

AF XY:

0.225

AC XY:

16679

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.249

Gnomad4 AMR

AF:

0.253

Gnomad4 ASJ

AF:

0.289

Gnomad4 EAS

AF:

0.0397

Gnomad4 SAS

AF:

0.169

Gnomad4 FIN

AF:

0.164

Gnomad4 NFE

AF:

0.237

Gnomad4 OTH

AF:

0.241

Alfa

AF:

0.240

Hom.:

1162

Bravo

AF:

0.237

Asia WGS

AF:

0.121

AC:

421

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 30, 2015	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. -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 51% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 47. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Developmental and epileptic encephalopathy, 14;C3554306:Autosomal dominant nocturnal frontal lobe epilepsy 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Developmental and epileptic encephalopathy, 14

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Autosomal dominant nocturnal frontal lobe epilepsy 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.2

DANN

Benign

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over