9-135784482-GCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCC-GCTCCCTCC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS1

The NM_020822.3(KCNT1):c.2944-30_2944-7del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00188 in 393,236 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0091 (12 hom., cov: 0)
  • Exomes 𝑓: 0.0019 (7 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNT1 NM_020822.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 9-135784482-GCTCCCTCCCTCCCTCCCTCCCTCC-G is Benign according to our data. Variant chr9-135784482-GCTCCCTCCCTCCCTCCCTCCCTCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 288487.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00188 (739/393236) while in subpopulation AFR AF= 0.0211 (241/11428). AF 95% confidence interval is 0.0189. There are 7 homozygotes in gnomad4_exome. There are 383 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNT1	NM_020822.3	c.2944-30_2944-7del		intron_variant		ENST00000371757.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNT1	ENST00000371757.7	c.2944-30_2944-7del		intron_variant		1	NM_020822.3	A2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 620 AN: 67764 Hom.: 12 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0337

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00212

Gnomad ASJ AF: 0.000914

Gnomad EAS AF: 0.00518

Gnomad SAS AF: 0.00351

Gnomad FIN AF: 0.000302

Gnomad MID AF: 0.00769

Gnomad NFE AF: 0.00173

Gnomad OTH AF: 0.00337

GnomAD4 exome AF: 0.00188 AC: 739 AN: 393236 Hom.: 7 AF XY: 0.00183 AC XY: 383 AN XY: 208924

Gnomad4 AFR exome AF: 0.0211

Gnomad4 AMR exome AF: 0.00236

Gnomad4 ASJ exome AF: 0.000644

Gnomad4 EAS exome AF: 0.000943

Gnomad4 SAS exome AF: 0.00178

Gnomad4 FIN exome AF: 0.000570

Gnomad4 NFE exome AF: 0.00121

Gnomad4 OTH exome AF: 0.00191

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00914 AC: 620 AN: 67824 Hom.: 12 Cov.: 0 AF XY: 0.00945 AC XY: 297 AN XY: 31412

Gnomad4 AFR AF: 0.0336

Gnomad4 AMR AF: 0.00212

Gnomad4 ASJ AF: 0.000914

Gnomad4 EAS AF: 0.00522

Gnomad4 SAS AF: 0.00352

Gnomad4 FIN AF: 0.000302

Gnomad4 NFE AF: 0.00173

Gnomad4 OTH AF: 0.00335

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jun 13, 2016

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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;