Variant 9-135784482-GCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCC-GCTCCCTCCCTCCCTCCCTCC 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.2944-18_2944-7del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 412 hom., cov: 0)

Exomes 𝑓: 0.063 ( 676 hom. )

Failed GnomAD Quality Control

Consequence

KCNT1
NM_020822.3 intron

Scores

Not classified

Clinical Significance

Benign/Likely 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-GCTCCCTCCCTCC-G is Benign according to our data. Variant chr9-135784482-GCTCCCTCCCTCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 195981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNT1	NM_020822.3 linkuse as main transcript	c.2944-18_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.2944-18_2944-7del		intron_variant		1	NM_020822.3	A2	Q5JUK3-3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

6843

AN:

67722

Hom.:

413

Cov.:

FAILED QC

Gnomad AFR

AF:

0.192

Gnomad AMI

AF:

0.0510

Gnomad AMR

AF:

0.0698

Gnomad ASJ

AF:

0.0723

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.0781

Gnomad NFE

AF:

0.0634

Gnomad OTH

AF:

0.0890

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0629

AC:

24367

AN:

387478

Hom.:

676

AF XY:

0.0614

AC XY:

12652

AN XY:

205896

show subpopulations

Gnomad4 AFR exome

AF:

0.145

Gnomad4 AMR exome

AF:

0.0339

Gnomad4 ASJ exome

AF:

0.0540

Gnomad4 EAS exome

AF:

0.0733

Gnomad4 SAS exome

AF:

0.0554

Gnomad4 FIN exome

AF:

0.143

Gnomad4 NFE exome

AF:

0.0515

Gnomad4 OTH exome

AF:

0.0669

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.101

AC:

6850

AN:

67784

Hom.:

412

Cov.:

AF XY:

0.103

AC XY:

3242

AN XY:

31410

show subpopulations

Gnomad4 AFR

AF:

0.191

Gnomad4 AMR

AF:

0.0696

Gnomad4 ASJ

AF:

0.0723

Gnomad4 EAS

AF:

0.115

Gnomad4 SAS

AF:

0.107

Gnomad4 FIN

AF:

0.157

Gnomad4 NFE

AF:

0.0633

Gnomad4 OTH

AF:

0.0906

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 05, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 28, 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. -

KCNT1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 11, 2021

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). -

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

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