9-135784482-GCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCC-GCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_020822.3(KCNT1):c.2944-18_2944-7dup variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0024 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNT1 NM_020822.3 intron
• Clinical Significance: Not reported in ClinVar
• 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 -4 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00239 (939/392978) while in subpopulation EAS AF= 0.00451 (105/23282). AF 95% confidence interval is 0.00381. There are 1 homozygotes in gnomad4_exome. There are 467 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNT1	NM_020822.3	c.2944-18_2944-7dup		intron_variant		ENST00000371757.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNT1	ENST00000371757.7	c.2944-18_2944-7dup		intron_variant		1	NM_020822.3	A2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 70 AN: 67738 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.000646

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00226

Gnomad ASJ AF: 0.000914

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00176

Gnomad FIN AF: 0.00181

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000952

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00239 AC: 939 AN: 392978 Hom.: 1 Cov.: 0 AF XY: 0.00224 AC XY: 467 AN XY: 208808

Gnomad4 AFR exome AF: 0.00315

Gnomad4 AMR exome AF: 0.000774

Gnomad4 ASJ exome AF: 0.00264

Gnomad4 EAS exome AF: 0.00451

Gnomad4 SAS exome AF: 0.000152

Gnomad4 FIN exome AF: 0.00164

Gnomad4 NFE exome AF: 0.00277

Gnomad4 OTH exome AF: 0.00324

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00103 AC: 70 AN: 67798 Hom.: 0 Cov.: 0 AF XY: 0.00108 AC XY: 34 AN XY: 31396

Gnomad4 AFR AF: 0.000643

Gnomad4 AMR AF: 0.00226

Gnomad4 ASJ AF: 0.000914

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00176

Gnomad4 FIN AF: 0.00181

Gnomad4 NFE AF: 0.000953

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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;