9-135784482-GCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCC-GCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCC

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_2944-7dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (19 hom., cov: 0)
  • Exomes 𝑓: 0.047 (187 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNT1 NM_020822.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 9-135784482-G-GCTCC is Benign according to our data. Variant chr9-135784482-G-GCTCC is described in ClinVar as [Benign]. Clinvar id is 3038164.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2326 AN: 67098 Hom.: 19 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0307

Gnomad AMI AF: 0.0155

Gnomad AMR AF: 0.0342

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.0568

Gnomad SAS AF: 0.0520

Gnomad FIN AF: 0.0437

Gnomad MID AF: 0.0308

Gnomad NFE AF: 0.0345

Gnomad OTH AF: 0.0421

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0469 AC: 18125 AN: 386440 Hom.: 187 Cov.: 0 AF XY: 0.0455 AC XY: 9333 AN XY: 205216

Gnomad4 AFR exome AF: 0.0483

Gnomad4 AMR exome AF: 0.0245

Gnomad4 ASJ exome AF: 0.0351

Gnomad4 EAS exome AF: 0.0835

Gnomad4 SAS exome AF: 0.0180

Gnomad4 FIN exome AF: 0.0428

Gnomad4 NFE exome AF: 0.0520

Gnomad4 OTH exome AF: 0.0541

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0347 AC: 2327 AN: 67156 Hom.: 19 Cov.: 0 AF XY: 0.0357 AC XY: 1110 AN XY: 31114

Gnomad4 AFR AF: 0.0310

Gnomad4 AMR AF: 0.0340

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.0551

Gnomad4 SAS AF: 0.0533

Gnomad4 FIN AF: 0.0437

Gnomad4 NFE AF: 0.0345

Gnomad4 OTH AF: 0.0419

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

KCNT1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 12, 2023

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

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;