NM_020822.3:c.2427G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020822.3(KCNT1):c.2427G>A(p.Thr809Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 1,613,708 control chromosomes in the GnomAD database, including 372,007 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 32274 hom., cov: 33)

Exomes 𝑓: 0.68 ( 339733 hom. )

Consequence

KCNT1
NM_020822.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -3.94

Publications

22 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
malignant migrating partial seizures of infancy
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 9-135777415-G-A is Benign according to our data. Variant chr9-135777415-G-A is described in ClinVar as Benign. ClinVar VariationId is 129357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.94 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020822.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNT1	NM_020822.3	MANE Select	c.2427G>A	p.Thr809Thr	synonymous	Exon 21 of 31	NP_065873.2	Q5JUK3-3
	KCNT1	NM_001272003.2		c.2292G>A	p.Thr764Thr	synonymous	Exon 20 of 31	NP_001258932.1	Q5JUK3-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCNT1	ENST00000371757.7	TSL:1 MANE Select	c.2427G>A	p.Thr809Thr	synonymous	Exon 21 of 31	ENSP00000360822.2	Q5JUK3-3
KCNT1	ENST00000460750.5	TSL:1	n.*2037G>A		non_coding_transcript_exon	Exon 21 of 32	ENSP00000418777.1	F8WC49
KCNT1	ENST00000460750.5	TSL:1	n.*2037G>A		3_prime_UTR	Exon 21 of 32	ENSP00000418777.1	F8WC49

Frequencies

GnomAD3 genomes

AF:

0.647

AC:

98304

AN:

151916

Hom.:

32246

Cov.:

show subpopulations

Gnomad AFR

AF:

0.567

Gnomad AMI

AF:

0.796

Gnomad AMR

AF:

0.663

Gnomad ASJ

AF:

0.488

Gnomad EAS

AF:

0.588

Gnomad SAS

AF:

0.751

Gnomad FIN

AF:

0.766

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.679

Gnomad OTH

AF:

0.613

GnomAD2 exomes

AF:

0.668

AC:

167817

AN:

251278

AF XY:

0.671

show subpopulations

Gnomad AFR exome

AF:

0.557

Gnomad AMR exome

AF:

0.659

Gnomad ASJ exome

AF:

0.496

Gnomad EAS exome

AF:

0.592

Gnomad FIN exome

AF:

0.764

Gnomad NFE exome

AF:

0.675

Gnomad OTH exome

AF:

0.645

GnomAD4 exome

AF:

0.679

AC:

993200

AN:

1461674

Hom.:

339733

Cov.:

AF XY:

0.681

AC XY:

495342

AN XY:

727164

show subpopulations

African (AFR)

AF:

0.562

AC:

18818

AN:

33470

American (AMR)

AF:

0.658

AC:

29417

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.491

AC:

12835

AN:

26124

East Asian (EAS)

AF:

0.576

AC:

22863

AN:

39698

South Asian (SAS)

AF:

0.738

AC:

63674

AN:

86254

European-Finnish (FIN)

AF:

0.766

AC:

40883

AN:

53406

Middle Eastern (MID)

AF:

0.507

AC:

2923

AN:

5766

European-Non Finnish (NFE)

AF:

0.686

AC:

762405

AN:

1111874

Other (OTH)

AF:

0.652

AC:

39382

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

17187

34374

51560

68747

85934

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19484

38968

58452

77936

97420

<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:

0.647

AC:

98378

AN:

152034

Hom.:

32274

Cov.:

AF XY:

0.651

AC XY:

48364

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.567

AC:

23506

AN:

41432

American (AMR)

AF:

0.663

AC:

10139

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.488

AC:

1692

AN:

3470

East Asian (EAS)

AF:

0.588

AC:

3030

AN:

5156

South Asian (SAS)

AF:

0.751

AC:

3617

AN:

4818

European-Finnish (FIN)

AF:

0.766

AC:

8123

AN:

10608

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.679

AC:

46121

AN:

67946

Other (OTH)

AF:

0.616

AC:

1300

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1840

3679

5519

7358

9198

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

802

1604

2406

3208

4010

<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:

0.656

Hom.:

72215

Bravo

AF:

0.630

Asia WGS

AF:

0.667

AC:

2320

AN:

3478

EpiCase

AF:

0.659

EpiControl

AF:

0.642

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (7)

not provided (2)

Autosomal dominant nocturnal frontal lobe epilepsy 5 (1)

Developmental and epileptic encephalopathy, 14 (1)

Developmental and epileptic encephalopathy, 14;C3554306:Autosomal dominant nocturnal frontal lobe epilepsy 5 (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

1.0

(source)

DANN

Benign

0.84

PhyloP100

-3.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over