9-135784482-GCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCC-GCTCCCTCCCTCCCTCCCTCCCTCC

Variant summary

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

The NM_020822.3(KCNT1):c.2944-14_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 0.22 (1711 hom., cov: 0)
  • Exomes 𝑓: 0.18 (5242 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNT1 NM_020822.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.164

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP6: Variant 9-135784482-GCTCCCTCC-G is Benign according to our data. Variant chr9-135784482-GCTCCCTCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 195983.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	c.2944-14_2944-7del		intron_variant		ENST00000371757.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNT1	ENST00000371757.7	c.2944-14_2944-7del		intron_variant		1	NM_020822.3	A2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 14606 AN: 67456 Hom.: 1712 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.195

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.164

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.181 AC: 68917 AN: 380182 Hom.: 5242 AF XY: 0.177 AC XY: 35744 AN XY: 201674

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.0709

Gnomad4 ASJ exome AF: 0.149

Gnomad4 EAS exome AF: 0.190

Gnomad4 SAS exome AF: 0.108

Gnomad4 FIN exome AF: 0.173

Gnomad4 NFE exome AF: 0.211

Gnomad4 OTH exome AF: 0.187

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.216 AC: 14613 AN: 67520 Hom.: 1711 Cov.: 0 AF XY: 0.212 AC XY: 6640 AN XY: 31282

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.163

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Mar 24, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 31, 2017	- -

KCNT1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 21, 2020

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 20, 2023

See Variant Classification Assertion Criteria. -

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs55843930; hg19: chr9-138676328;