Variant 9-135784482-GCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCC-GCTCCCTCCCTCCCTCC 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.2944-22_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 0.021 ( 29 hom., cov: 0)

Exomes 𝑓: 0.014 ( 81 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-GCTCCCTCCCTCCCTCC-G is Benign according to our data. Variant chr9-135784482-GCTCCCTCCCTCCCTCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 286875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-135784482-GCTCCCTCCCTCCCTCC-G is described in Lovd as [Benign]. Variant chr9-135784482-GCTCCCTCCCTCCCTCC-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.2944-22_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.2944-22_2944-7del		intron_variant		1	NM_020822.3	A2	Q5JUK3-3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1393

AN:

67762

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0201

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0256

Gnomad ASJ

AF:

0.0183

Gnomad EAS

AF:

0.0119

Gnomad SAS

AF:

0.00937

Gnomad FIN

AF:

0.00816

Gnomad MID

AF:

0.0154

Gnomad NFE

AF:

0.0223

Gnomad OTH

AF:

0.0213

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0139

AC:

5479

AN:

392920

Hom.:

AF XY:

0.0139

AC XY:

2898

AN XY:

208770

show subpopulations

Gnomad4 AFR exome

AF:

0.0139

Gnomad4 AMR exome

AF:

0.00934

Gnomad4 ASJ exome

AF:

0.0138

Gnomad4 EAS exome

AF:

0.0155

Gnomad4 SAS exome

AF:

0.00707

Gnomad4 FIN exome

AF:

0.0107

Gnomad4 NFE exome

AF:

0.0164

Gnomad4 OTH exome

AF:

0.0116

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0205

AC:

1393

AN:

67822

Hom.:

Cov.:

AF XY:

0.0203

AC XY:

638

AN XY:

31414

show subpopulations

Gnomad4 AFR

AF:

0.0200

Gnomad4 AMR

AF:

0.0255

Gnomad4 ASJ

AF:

0.0183

Gnomad4 EAS

AF:

0.0120

Gnomad4 SAS

AF:

0.00939

Gnomad4 FIN

AF:

0.00816

Gnomad4 NFE

AF:

0.0223

Gnomad4 OTH

AF:

0.0212

ClinVar

Significance: Benign/Likely 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)

Apr 05, 2016

- -

KCNT1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 05, 2021

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 24, 2016

- -

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