NM_020822.3:c.3178-12_3178-3delTGCCCTGCCC

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_020822.3(KCNT1):c.3178-12_3178-3delTGCCCTGCCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000185 in 1,548,246 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00064 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

KCNT1
NM_020822.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

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: 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 -16 ACMG points.

BP6

Variant 9-135786170-CGCCCTGCCCT-C is Benign according to our data. Variant chr9-135786170-CGCCCTGCCCT-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 420320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000637 (96/150636) while in subpopulation AFR AF = 0.00189 (77/40750). AF 95% confidence interval is 0.00155. There are 0 homozygotes in GnomAd4. There are 53 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 96 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.3178-12_3178-3delTGCCCTGCCC		splice_region intron	N/A	NP_065873.2	Q5JUK3-3
	KCNT1	NM_001272003.2		c.3043-12_3043-3delTGCCCTGCCC		splice_region intron	N/A	NP_001258932.1	Q5JUK3-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KCNT1	ENST00000371757.7	TSL:1 MANE Select	c.3178-12_3178-3delTGCCCTGCCC	splice_region intron	N/A	ENSP00000360822.2	Q5JUK3-3
KCNT1	ENST00000460750.5	TSL:1	n.2788-12_2788-3delTGCCCTGCCC	splice_region intron	N/A	ENSP00000418777.1	F8WC49
KCNT1	ENST00000487664.5	TSL:5	c.3178-12_3178-3delTGCCCTGCCC	splice_region intron	N/A	ENSP00000417851.2	Q5JUK3-2

Frequencies

GnomAD3 genomes

AF:

0.000638

AC:

AN:

150522

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00190

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000592

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:

0.000133

Gnomad OTH

AF:

0.000484

GnomAD2 exomes

AF:

0.000213

AC:

AN:

197052

AF XY:

0.000228

show subpopulations

Gnomad AFR exome

AF:

0.00145

Gnomad AMR exome

AF:

0.000220

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000538

Gnomad NFE exome

AF:

0.000218

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000136

AC:

190

AN:

1397610

Hom.:

AF XY:

0.000139

AC XY:

AN XY:

696448

show subpopulations

African (AFR)

AF:

0.00206

AC:

AN:

30558

American (AMR)

AF:

0.000180

AC:

AN:

38862

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25146

East Asian (EAS)

AF:

0.00

AC:

AN:

38612

South Asian (SAS)

AF:

0.0000732

AC:

AN:

81930

European-Finnish (FIN)

AF:

0.0000396

AC:

AN:

50460

Middle Eastern (MID)

AF:

0.000179

AC:

AN:

5596

European-Non Finnish (NFE)

AF:

0.0000927

AC:

AN:

1068454

Other (OTH)

AF:

0.000207

AC:

AN:

57992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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:

0.000637

AC:

AN:

150636

Hom.:

Cov.:

AF XY:

0.000720

AC XY:

AN XY:

73582

show subpopulations

African (AFR)

AF:

0.00189

AC:

AN:

40750

American (AMR)

AF:

0.000592

AC:

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5068

South Asian (SAS)

AF:

0.00

AC:

AN:

4744

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10472

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000133

AC:

AN:

67644

Other (OTH)

AF:

0.000479

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

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:

0.00

Hom.:

365

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

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)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over