9-135784603-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_020822.3(KCNT1):c.3012G>A(p.Ser1004Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000028 in 1,608,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

KCNT1
NM_020822.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.00

Publications

0 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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 9-135784603-G-A is Benign according to our data. Variant chr9-135784603-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 579818.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5 with no splicing effect.

BS2

High AC in GnomAdExome4 at 43 AD gene.

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.3012G>A	p.Ser1004Ser	synonymous	Exon 26 of 31	NP_065873.2	Q5JUK3-3
	KCNT1	NM_001272003.2		c.2877G>A	p.Ser959Ser	synonymous	Exon 25 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.3012G>A	p.Ser1004Ser	synonymous	Exon 26 of 31	ENSP00000360822.2	Q5JUK3-3
KCNT1	ENST00000460750.5	TSL:1	n.*2622G>A		non_coding_transcript_exon	Exon 26 of 32	ENSP00000418777.1	F8WC49
KCNT1	ENST00000460750.5	TSL:1	n.*2622G>A		3_prime_UTR	Exon 26 of 32	ENSP00000418777.1	F8WC49

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150620

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000488

AC:

AN:

246034

AF XY:

0.0000224

show subpopulations

Gnomad AFR exome

AF:

0.000128

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000271

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000295

AC:

AN:

1458078

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

725328

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33424

American (AMR)

AF:

0.00

AC:

AN:

44602

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26046

East Asian (EAS)

AF:

0.000126

AC:

AN:

39564

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86142

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52122

Middle Eastern (MID)

AF:

0.000198

AC:

AN:

5044

European-Non Finnish (NFE)

AF:

0.0000288

AC:

AN:

1110986

Other (OTH)

AF:

0.0000333

AC:

AN:

60148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000133

AC:

AN:

150620

Hom.:

Cov.:

AF XY:

0.0000272

AC XY:

AN XY:

73428

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40916

American (AMR)

AF:

0.00

AC:

AN:

15072

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5070

South Asian (SAS)

AF:

0.00

AC:

AN:

4750

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10294

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67760

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000774

Hom.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

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)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.59

(source)

DANN

Benign

0.51

PhyloP100

-5.0

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Computational scores

Splicing

Publications

Other links and lift over