9-135784482-GCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCC-GCTCCCTCCCTCCCTCCCTCCCTCCCTCC

Variant summary

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

The NM_020822.3(KCNT1):c.2944-10_2944-7del variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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-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_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNT1	NM_020822.3	c.2944-10_2944-7del		intron_variant		ENST00000371757.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNT1	ENST00000371757.7	c.2944-10_2944-7del		intron_variant		1	NM_020822.3	A2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 8675 AN: 67370 Hom.: 715 Cov.: 0 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

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.: 0 AF XY: 0.131 AC XY: 4088 AN XY: 31242

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, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Mar 03, 2017

- -

KCNT1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 12, 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). -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs55843930; hg19: chr9-138676328;