rs17038714

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1749G>A(p.Ala583Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,612,168 control chromosomes in the GnomAD database, including 50,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A583A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.30 ( 7877 hom., cov: 34)

Exomes 𝑓: 0.23 ( 42580 hom. )

Consequence

KCNT1
NM_020822.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.68

Publications

17 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 9-135770427-G-A is Benign according to our data. Variant chr9-135770427-G-A is described in ClinVar as Benign. ClinVar VariationId is 129353.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.68 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.463 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNT1	NM_020822.3	MANE Select	c.1749G>A	p.Ala583Ala	synonymous	Exon 17 of 31	NP_065873.2
	KCNT1	NM_001272003.2		c.1614G>A	p.Ala538Ala	synonymous	Exon 16 of 31	NP_001258932.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KCNT1	ENST00000371757.7	TSL:1 MANE Select	c.1749G>A	p.Ala583Ala	synonymous	Exon 17 of 31	ENSP00000360822.2
KCNT1	ENST00000460750.5	TSL:1	n.*1359G>A		non_coding_transcript_exon	Exon 17 of 32	ENSP00000418777.1
KCNT1	ENST00000460750.5	TSL:1	n.*1359G>A		3_prime_UTR	Exon 17 of 32	ENSP00000418777.1

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

45412

AN:

152056

Hom.:

7858

Cov.:

show subpopulations

Gnomad AFR

AF:

0.468

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.156

Gnomad EAS

AF:

0.417

Gnomad SAS

AF:

0.354

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.212

Gnomad OTH

AF:

0.250

GnomAD2 exomes

AF:

0.259

AC:

64505

AN:

249284

AF XY:

0.256

show subpopulations

Gnomad AFR exome

AF:

0.481

Gnomad AMR exome

AF:

0.177

Gnomad ASJ exome

AF:

0.152

Gnomad EAS exome

AF:

0.420

Gnomad FIN exome

AF:

0.324

Gnomad NFE exome

AF:

0.208

Gnomad OTH exome

AF:

0.226

GnomAD4 exome

AF:

0.231

AC:

337040

AN:

1459994

Hom.:

42580

Cov.:

AF XY:

0.232

AC XY:

168726

AN XY:

726302

show subpopulations

African (AFR)

AF:

0.479

AC:

16026

AN:

33446

American (AMR)

AF:

0.181

AC:

8050

AN:

44590

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

4083

AN:

26038

East Asian (EAS)

AF:

0.437

AC:

17334

AN:

39684

South Asian (SAS)

AF:

0.317

AC:

27270

AN:

86120

European-Finnish (FIN)

AF:

0.317

AC:

16712

AN:

52794

Middle Eastern (MID)

AF:

0.152

AC:

877

AN:

5762

European-Non Finnish (NFE)

AF:

0.209

AC:

232453

AN:

1111248

Other (OTH)

AF:

0.236

AC:

14235

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

13702

27403

41105

54806

68508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8318

16636

24954

33272

41590

<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:

0.299

AC:

45470

AN:

152174

Hom.:

7877

Cov.:

AF XY:

0.303

AC XY:

22572

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.468

AC:

19435

AN:

41492

American (AMR)

AF:

0.207

AC:

3174

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

543

AN:

3472

East Asian (EAS)

AF:

0.417

AC:

2152

AN:

5162

South Asian (SAS)

AF:

0.354

AC:

1707

AN:

4828

European-Finnish (FIN)

AF:

0.316

AC:

3358

AN:

10610

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.212

AC:

14404

AN:

67992

Other (OTH)

AF:

0.254

AC:

537

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1576

3152

4728

6304

7880

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

456

912

1368

1824

2280

<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:

0.248

Hom.:

3652

Bravo

AF:

0.297

Asia WGS

AF:

0.388

AC:

1349

AN:

3478

EpiCase

AF:

0.195

EpiControl

AF:

0.189

ClinVar

ClinVar submissions as Germline

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

-0.51

CADD

Benign

9.5

(source)

DANN

Benign

0.93

PhyloP100

-1.7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over