Genetic Variant KCNT1:c.2944-10_2944-7delCCCT (chr9-135784482-GCTCC-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_020822.3(KCNT1):c.2944-10_2944-7delCCCT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.13 ( 719 hom., cov: 0)

Exomes 𝑓: 0.12 ( 2854 hom. )

Failed GnomAD Quality Control

Consequence

KCNT1
NM_020822.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.164

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 Likely_benign. Variant got -2 ACMG points.

BP6

Variant 9-135784482-GCTCC-G is Benign according to our data. Variant chr9-135784482-GCTCC-G is described in ClinVar as [Benign]. Clinvar id is 195984.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNT1	NM_020822.3 link	c.2944-10_2944-7delCCCT		splice_region_variant, intron_variant	Intron 25 of 30	ENST00000371757.7	NP_065873.2	Q5JUK3-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNT1	ENST00000371757.7 link	c.2944-52_2944-49delCTCC		intron_variant	Intron 25 of 30	1	NM_020822.3	ENSP00000360822.2		Q5JUK3-3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

8675

AN:

67370

Hom.:

715

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0922

Gnomad AMI

AF:

0.210

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.125

Gnomad EAS

AF:

0.197

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.177

Gnomad MID

AF:

0.115

Gnomad NFE

AF:

0.125

Gnomad OTH

AF:

0.151

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.124

AC:

47673

AN:

383914

Hom.:

2854

AF XY:

0.121

AC XY:

24726

AN XY:

203820

show subpopulations

Gnomad4 AFR exome

AF:

0.0931

Gnomad4 AMR exome

AF:

0.108

Gnomad4 ASJ exome

AF:

0.114

Gnomad4 EAS exome

AF:

0.202

Gnomad4 SAS exome

AF:

0.0614

Gnomad4 FIN exome

AF:

0.149

Gnomad4 NFE exome

AF:

0.128

Gnomad4 OTH exome

AF:

0.138

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.129

AC:

8687

AN:

67428

Hom.:

719

Cov.:

AF XY:

0.131

AC XY:

4088

AN XY:

31242

show subpopulations

Gnomad4 AFR

AF:

0.0926

Gnomad4 AMR

AF:

0.184

Gnomad4 ASJ

AF:

0.125

Gnomad4 EAS

AF:

0.197

Gnomad4 SAS

AF:

0.116

Gnomad4 FIN

AF:

0.177

Gnomad4 NFE

AF:

0.125

Gnomad4 OTH

AF:

0.150

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 03, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

KCNT1-related disorder

Benign:1

Feb 12, 2021

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

9-135784482-GCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCC-GCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCC

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