Variant rs759060806 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_020822.3(KCNT1):c.2944-19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.051 ( 0 hom., cov: 0)

Exomes 𝑓: 0.15 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KCNT1
NM_020822.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.369

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 9-135784516-T-C is Benign according to our data. Variant chr9-135784516-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 445520.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.2944-19T>C		intron_variant		ENST00000371757.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNT1	ENST00000371757.7 linkuse as main transcript	c.2944-19T>C		intron_variant		1	NM_020822.3	A2	Q5JUK3-3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1176

AN:

22810

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0421

Gnomad AMI

AF:

0.0556

Gnomad AMR

AF:

0.0404

Gnomad ASJ

AF:

0.0500

Gnomad EAS

AF:

0.0294

Gnomad SAS

AF:

0.0348

Gnomad FIN

AF:

0.0807

Gnomad MID

AF:

0.0769

Gnomad NFE

AF:

0.0586

Gnomad OTH

AF:

0.0467

GnomAD3 exomes

AF:

0.122

AC:

4388

AN:

35912

Hom.:

AF XY:

0.118

AC XY:

2266

AN XY:

19262

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.244

Gnomad ASJ exome

AF:

0.0520

Gnomad EAS exome

AF:

0.272

Gnomad SAS exome

AF:

0.138

Gnomad FIN exome

AF:

0.0199

Gnomad NFE exome

AF:

0.124

Gnomad OTH exome

AF:

0.159

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.149

AC:

18140

AN:

121982

Hom.:

Cov.:

AF XY:

0.152

AC XY:

10010

AN XY:

65644

show subpopulations

Gnomad4 AFR exome

AF:

0.0766

Gnomad4 AMR exome

AF:

0.174

Gnomad4 ASJ exome

AF:

0.0771

Gnomad4 EAS exome

AF:

0.0563

Gnomad4 SAS exome

AF:

0.247

Gnomad4 FIN exome

AF:

0.0563

Gnomad4 NFE exome

AF:

0.163

Gnomad4 OTH exome

AF:

0.150

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0514

AC:

1176

AN:

22860

Hom.:

Cov.:

AF XY:

0.0484

AC XY:

554

AN XY:

11440

show subpopulations

Gnomad4 AFR

AF:

0.0418

Gnomad4 AMR

AF:

0.0403

Gnomad4 ASJ

AF:

0.0500

Gnomad4 EAS

AF:

0.0293

Gnomad4 SAS

AF:

0.0345

Gnomad4 FIN

AF:

0.0807

Gnomad4 NFE

AF:

0.0586

Gnomad4 OTH

AF:

0.0462

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 29, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 15, 2019	- -

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

BayesDel_noAF

Benign

-0.94

CADD

Benign

4.6

DANN

Benign

0.40

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