9-135784482-GCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCC-GCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCC

Variant names:

• chr9-135784482-G-GCTCCCTCC
• rs55843930
• NM_020822.3:c.2944-14_2944-7dupCCCTCCCT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_020822.3(KCNT1):​c.2944-14_2944-7dupCCCTCCCT variant causes a splice region, 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 0.0052 (0 hom., cov: 0)
  • Exomes 𝑓: 0.011 (16 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNT1 NM_020822.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• childhood-onset epilepsy syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy, 14

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• malignant migrating partial seizures of infancy

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• autosomal dominant nocturnal frontal lobe epilepsy 5

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal dominant nocturnal frontal lobe epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020822.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNT1	NM_020822.3	MANE Select	c.2944-14_2944-7dupCCCTCCCT		splice_region intron	N/A	NP_065873.2
	KCNT1	NM_001272003.2		c.2809-14_2809-7dupCCCTCCCT		splice_region intron	N/A	NP_001258932.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNT1	ENST00000371757.7	TSL:1 MANE Select	c.2944-14_2944-7dupCCCTCCCT		splice_region intron	N/A	ENSP00000360822.2
	KCNT1	ENST00000460750.5	TSL:1	n.*2554-14_*2554-7dupCCCTCCCT		splice_region intron	N/A	ENSP00000418777.1
	KCNT1	ENST00000487664.5	TSL:5	c.2944-14_2944-7dupCCCTCCCT		splice_region intron	N/A	ENSP00000417851.2

Frequencies

GnomAD3 genomes AF: 0.00520 AC: 352 AN: 67664 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00492

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00608

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00571

Gnomad SAS AF: 0.00589

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.0154

Gnomad NFE AF: 0.00416

Gnomad OTH AF: 0.00225

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0111 AC: 4327 AN: 391482 Hom.: 16 Cov.: 0 AF XY: 0.0105 AC XY: 2193 AN XY: 208040

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0148 AC: 168 AN: 11372

American (AMR) AF: 0.00560 AC: 130 AN: 23218

Ashkenazi Jewish (ASJ) AF: 0.0142 AC: 197 AN: 13902

East Asian (EAS) AF: 0.0133 AC: 309 AN: 23236

South Asian (SAS) AF: 0.00219 AC: 101 AN: 46058

European-Finnish (FIN) AF: 0.0116 AC: 345 AN: 29692

Middle Eastern (MID) AF: 0.0121 AC: 21 AN: 1732

European-Non Finnish (NFE) AF: 0.0126 AC: 2772 AN: 220414

Other (OTH) AF: 0.0130 AC: 284 AN: 21858

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00515 AC: 349 AN: 67724 Hom.: 0 Cov.: 0 AF XY: 0.00615 AC XY: 193 AN XY: 31372

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00496 AC: 77 AN: 15530

American (AMR) AF: 0.00593 AC: 42 AN: 7080

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 22 AN: 2186

East Asian (EAS) AF: 0.00522 AC: 10 AN: 1914

South Asian (SAS) AF: 0.00531 AC: 9 AN: 1694

European-Finnish (FIN) AF: 0.0127 AC: 42 AN: 3304

Middle Eastern (MID) AF: 0.0164 AC: 2 AN: 122

European-Non Finnish (NFE) AF: 0.00413 AC: 143 AN: 34606

Other (OTH) AF: 0.00223 AC: 2 AN: 896

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs55843930; hg19: chr9-138676328;