chr9-135786170-CGCCCT-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_020822.3(KCNT1):c.3178-7_3178-3delTGCCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,544,516 control chromosomes in the GnomAD database, including 46,499 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7356 hom., cov: 0)

Exomes 𝑓: 0.24 ( 39143 hom. )

Consequence

KCNT1
NM_020822.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.02

Publications

1 publications found

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 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, 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

KCNT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 9-135786170-CGCCCT-C is Benign according to our data. Variant chr9-135786170-CGCCCT-C is described in ClinVar as Benign. ClinVar VariationId is 196184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNT1	NM_020822.3 link	c.3178-7_3178-3delTGCCC		splice_region_variant, intron_variant	Intron 28 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.3178-7_3178-3delTGCCC		splice_region_variant, intron_variant	Intron 28 of 30	1	NM_020822.3	ENSP00000360822.2		Q5JUK3-3

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

44648

AN:

150376

Hom.:

7328

Cov.:

show subpopulations

Gnomad AFR

AF:

0.450

Gnomad AMI

AF:

0.192

Gnomad AMR

AF:

0.240

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.253

Gnomad SAS

AF:

0.259

Gnomad FIN

AF:

0.147

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.253

Gnomad OTH

AF:

0.285

GnomAD2 exomes

AF:

0.242

AC:

47644

AN:

197052

AF XY:

0.244

show subpopulations

Gnomad AFR exome

AF:

0.444

Gnomad AMR exome

AF:

0.191

Gnomad ASJ exome

AF:

0.196

Gnomad EAS exome

AF:

0.257

Gnomad FIN exome

AF:

0.152

Gnomad NFE exome

AF:

0.246

Gnomad OTH exome

AF:

0.245

GnomAD4 exome

AF:

0.243

AC:

338211

AN:

1394026

Hom.:

39143

AF XY:

0.244

AC XY:

169621

AN XY:

694772

show subpopulations

African (AFR)

AF:

0.433

AC:

13205

AN:

30474

American (AMR)

AF:

0.197

AC:

7639

AN:

38780

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

4933

AN:

25120

East Asian (EAS)

AF:

0.239

AC:

9224

AN:

38564

South Asian (SAS)

AF:

0.273

AC:

22312

AN:

81806

European-Finnish (FIN)

AF:

0.159

AC:

7999

AN:

50424

Middle Eastern (MID)

AF:

0.249

AC:

1390

AN:

5586

European-Non Finnish (NFE)

AF:

0.241

AC:

257073

AN:

1065412

Other (OTH)

AF:

0.249

AC:

14436

AN:

57860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

11963

23926

35890

47853

59816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8750

17500

26250

35000

43750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.297

AC:

44722

AN:

150490

Hom.:

7356

Cov.:

AF XY:

0.290

AC XY:

21328

AN XY:

73492

show subpopulations

African (AFR)

AF:

0.451

AC:

18339

AN:

40688

American (AMR)

AF:

0.241

AC:

3656

AN:

15200

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

713

AN:

3466

East Asian (EAS)

AF:

0.254

AC:

1285

AN:

5066

South Asian (SAS)

AF:

0.259

AC:

1228

AN:

4734

European-Finnish (FIN)

AF:

0.147

AC:

1541

AN:

10462

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.253

AC:

17115

AN:

67594

Other (OTH)

AF:

0.282

AC:

589

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1404

2808

4213

5617

7021

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

452

904

1356

1808

2260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.156

Hom.:

365

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Mar 31, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 42% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 39. Only high quality variants are reported. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Developmental and epileptic encephalopathy, 14;C3554306:Autosomal dominant nocturnal frontal lobe epilepsy 5

Benign:1

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jan 04, 2016

GeneDx

Significance: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:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over