9-135784482-GCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCC-GCTCCCTCCCTCCCTCCCTCCCTCCCTCC

Variant names:

• chr9-135784482-GCTCCCTCCCTCC-G
• rs55843930
• NM_020822.3:c.2944-18_2944-7delCCCTCCCTCCCT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_020822.3(KCNT1):​c.2944-18_2944-7delCCCTCCCTCCCT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (412 hom., cov: 0)
  • Exomes 𝑓: 0.063 (676 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNT1 NM_020822.3 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• 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 -8 ACMG points.

• BP6: Variant 9-135784482-GCTCCCTCCCTCC-G is Benign according to our data. Variant chr9-135784482-GCTCCCTCCCTCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 195981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNT1	NM_020822.3	c.2944-18_2944-7delCCCTCCCTCCCT		splice_region_variant, intron_variant	Intron 25 of 30	ENST00000371757.7	NP_065873.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNT1	ENST00000371757.7	c.2944-52_2944-41delCTCCCTCCCTCC		intron_variant	Intron 25 of 30	1	NM_020822.3	ENSP00000360822.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 6843 AN: 67722 Hom.: 413 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.0510

Gnomad AMR AF: 0.0698

Gnomad ASJ AF: 0.0723

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.0781

Gnomad NFE AF: 0.0634

Gnomad OTH AF: 0.0890

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0629 AC: 24367 AN: 387478 Hom.: 676 AF XY: 0.0614 AC XY: 12652 AN XY: 205896

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.0339

Gnomad4 ASJ exome AF: 0.0540

Gnomad4 EAS exome AF: 0.0733

Gnomad4 SAS exome AF: 0.0554

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.0515

Gnomad4 OTH exome AF: 0.0669

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.101 AC: 6850 AN: 67784 Hom.: 412 Cov.: 0 AF XY: 0.103 AC XY: 3242 AN XY: 31410

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.0696

Gnomad4 ASJ AF: 0.0723

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.0633

Gnomad4 OTH AF: 0.0906

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Apr 28, 2017

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Apr 05, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

KCNT1-related disorder Benign:1

Feb 11, 2021

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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). -

Developmental and epileptic encephalopathy, 14 Benign:1

Mar 15, 2022

Genome-Nilou Lab

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal dominant nocturnal frontal lobe epilepsy 5 Benign:1

Mar 15, 2022

Genome-Nilou Lab

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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;