Variant 9-135784482-GCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCC-GCTCCCTCCCTCC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_020822.3(KCNT1):c.2944-26_2944-7del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 523 hom., cov: 0)

Exomes 𝑓: 0.10 ( 2098 hom. )

Failed GnomAD Quality Control

Consequence

KCNT1
NM_020822.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.81

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP6

Variant 9-135784482-GCTCCCTCCCTCCCTCCCTCC-G is Benign according to our data. Variant chr9-135784482-GCTCCCTCCCTCCCTCCCTCC-G is described in ClinVar as [Benign]. Clinvar id is 195980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-135784482-GCTCCCTCCCTCCCTCCCTCC-G is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNT1	NM_020822.3 linkuse as main transcript	c.2944-26_2944-7del		intron_variant		ENST00000371757.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNT1	ENST00000371757.7 linkuse as main transcript	c.2944-26_2944-7del		intron_variant		1	NM_020822.3	A2	Q5JUK3-3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

9351

AN:

67836

Hom.:

524

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0720

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.295

Gnomad EAS

AF:

0.0331

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.0845

Gnomad MID

AF:

0.308

Gnomad NFE

AF:

0.164

Gnomad OTH

AF:

0.165

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.103

AC:

40468

AN:

392740

Hom.:

2098

AF XY:

0.102

AC XY:

21309

AN XY:

208668

show subpopulations

Gnomad4 AFR exome

AF:

0.0444

Gnomad4 AMR exome

AF:

0.0778

Gnomad4 ASJ exome

AF:

0.217

Gnomad4 EAS exome

AF:

0.0203

Gnomad4 SAS exome

AF:

0.0815

Gnomad4 FIN exome

AF:

0.0842

Gnomad4 NFE exome

AF:

0.116

Gnomad4 OTH exome

AF:

0.110

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.138

AC:

9350

AN:

67896

Hom.:

523

Cov.:

AF XY:

0.136

AC XY:

4281

AN XY:

31454

show subpopulations

Gnomad4 AFR

AF:

0.0719

Gnomad4 AMR

AF:

0.156

Gnomad4 ASJ

AF:

0.295

Gnomad4 EAS

AF:

0.0334

Gnomad4 SAS

AF:

0.126

Gnomad4 FIN

AF:

0.0845

Gnomad4 NFE

AF:

0.164

Gnomad4 OTH

AF:

0.163

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Feb 26, 2016

- -

KCNT1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 12, 2023

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 13, 2016

- -

Developmental and epileptic encephalopathy, 14

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

Autosomal dominant nocturnal frontal lobe epilepsy 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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