9-135784482-GCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCC-GCTCC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_020822.3(KCNT1):c.2944-34_2944-7del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0207 in 393,590 control chromosomes in the GnomAD database, including 569 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (63 hom., cov: 0)
  • Exomes 𝑓: 0.021 (569 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNT1 NM_020822.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.81

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 -16 ACMG points.

• BP6: Variant 9-135784482-GCTCCCTCCCTCCCTCCCTCCCTCCCTCC-G is Benign according to our data. Variant chr9-135784482-GCTCCCTCCCTCCCTCCCTCCCTCCCTCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 288488.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-135784482-GCTCCCTCCCTCCCTCCCTCCCTCCCTCC-G is described in Lovd as [Likely_benign].
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNT1	NM_020822.3	c.2944-34_2944-7del		intron_variant		ENST00000371757.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNT1	ENST00000371757.7	c.2944-34_2944-7del		intron_variant		1	NM_020822.3	A2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1489 AN: 67768 Hom.: 62 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00814

Gnomad AMI AF: 0.0587

Gnomad AMR AF: 0.0697

Gnomad ASJ AF: 0.00640

Gnomad EAS AF: 0.0922

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.00634

Gnomad MID AF: 0.00769

Gnomad NFE AF: 0.0117

Gnomad OTH AF: 0.0315

GnomAD4 exome AF: 0.0207 AC: 8147 AN: 393590 Hom.: 569 AF XY: 0.0227 AC XY: 4755 AN XY: 209112

Gnomad4 AFR exome AF: 0.00446

Gnomad4 AMR exome AF: 0.0764

Gnomad4 ASJ exome AF: 0.00349

Gnomad4 EAS exome AF: 0.0485

Gnomad4 SAS exome AF: 0.0623

Gnomad4 FIN exome AF: 0.00419

Gnomad4 NFE exome AF: 0.00783

Gnomad4 OTH exome AF: 0.0174

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0220 AC: 1494 AN: 67828 Hom.: 63 Cov.: 0 AF XY: 0.0244 AC XY: 766 AN XY: 31412

Gnomad4 AFR AF: 0.00810

Gnomad4 AMR AF: 0.0701

Gnomad4 ASJ AF: 0.00640

Gnomad4 EAS AF: 0.0924

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.00634

Gnomad4 NFE AF: 0.0117

Gnomad4 OTH AF: 0.0324

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jun 07, 2016

- -

Developmental and epileptic encephalopathy, 14 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 28, 2016

- -

Autosomal dominant nocturnal frontal lobe epilepsy 5 Benign:1

Likely 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;