Genetic Variant KCNT1:c.2944-34_2944-7delCCCTCCCTCCCTCCCTCCCTCCCTCCCT (chr9-135784482-GCTCCCTCCCTCCCTCCCTCCCTCCCTCC-G) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_020822.3(KCNT1):c.2944-34_2944-7delCCCTCCCTCCCTCCCTCCCTCCCTCCCT variant causes a splice region, 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 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.81

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
KCNT1	NM_020822.3 link	c.2944-34_2944-7delCCCTCCCTCCCTCCCTCCCTCCCTCCCT		splice_region_variant, intron_variant	Intron 25 of 30	ENST00000371757.7	NP_065873.2	Q5JUK3-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNT1	ENST00000371757.7 link	c.2944-52_2944-25delCTCCCTCCCTCCCTCCCTCCCTCCCTCC		intron_variant	Intron 25 of 30	1	NM_020822.3	ENSP00000360822.2		Q5JUK3-3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1489

AN:

67768

Hom.:

Cov.:

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

show subpopulations

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.:

Cov.:

AF XY:

0.0244

AC XY:

766

AN XY:

31412

show subpopulations

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

LINK: link

Submissions by phenotype

not specified

Benign:1

Jun 07, 2016

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Jan 28, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

9-135784482-GCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTCC-GCTCCCTCCCTCC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over