Variant chr9-135786170-C-CGCCCT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 8P and 16B. PVS1BP6_Very_StrongBS1BS2

The NM_020822.3(KCNT1):c.3178-7_3178-3dupTGCCC variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 3 hom., cov: 0)

Exomes 𝑓: 0.0063 ( 23 hom. )

Consequence

KCNT1
NM_020822.3 splice_acceptor, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.600

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 links:

KCNT1 (HGNC:):

KCNT1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.

BP6

Variant 9-135786170-C-CGCCCT is Benign according to our data. Variant chr9-135786170-C-CGCCCT is described in ClinVar as [Benign]. Clinvar id is 196185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00574 (865/150638) while in subpopulation AMR AF= 0.00868 (132/15210). AF 95% confidence interval is 0.00747. There are 3 homozygotes in gnomad4. There are 411 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High AC in GnomAd4 at 865 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNT1	NM_020822.3 linkuse as main transcript	c.3178-7_3178-3dupTGCCC		splice_acceptor_variant, intron_variant		ENST00000371757.7	NP_065873.2	Q5JUK3-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNT1	ENST00000371757.7 linkuse as main transcript	c.3178-7_3178-3dupTGCCC		splice_acceptor_variant, intron_variant		1	NM_020822.3	ENSP00000360822.2		Q5JUK3-3

Frequencies

GnomAD3 genomes

AF:

0.00575

AC:

865

AN:

150524

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00335

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00869

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00413

Gnomad SAS

AF:

0.00253

Gnomad FIN

AF:

0.00315

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00736

Gnomad OTH

AF:

0.00727

GnomAD3 exomes

AF:

0.00488

AC:

962

AN:

197052

Hom.:

AF XY:

0.00464

AC XY:

508

AN XY:

109482

show subpopulations

Gnomad AFR exome

AF:

0.00330

Gnomad AMR exome

AF:

0.00619

Gnomad ASJ exome

AF:

0.00331

Gnomad EAS exome

AF:

0.00414

Gnomad SAS exome

AF:

0.00262

Gnomad FIN exome

AF:

0.00274

Gnomad NFE exome

AF:

0.00601

Gnomad OTH exome

AF:

0.00593

GnomAD4 exome

AF:

0.00634

AC:

8863

AN:

1397248

Hom.:

Cov.:

AF XY:

0.00629

AC XY:

4377

AN XY:

696296

show subpopulations

Gnomad4 AFR exome

AF:

0.00324

Gnomad4 AMR exome

AF:

0.00708

Gnomad4 ASJ exome

AF:

0.00350

Gnomad4 EAS exome

AF:

0.00417

Gnomad4 SAS exome

AF:

0.00314

Gnomad4 FIN exome

AF:

0.00333

Gnomad4 NFE exome

AF:

0.00695

Gnomad4 OTH exome

AF:

0.00636

GnomAD4 genome

AF:

0.00574

AC:

865

AN:

150638

Hom.:

Cov.:

AF XY:

0.00559

AC XY:

411

AN XY:

73584

show subpopulations

Gnomad4 AFR

AF:

0.00334

Gnomad4 AMR

AF:

0.00868

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00414

Gnomad4 SAS

AF:

0.00253

Gnomad4 FIN

AF:

0.00315

Gnomad4 NFE

AF:

0.00736

Gnomad4 OTH

AF:

0.00719

Bravo

AF:

0.00608

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Mar 31, 2016

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 19, 2021

- -

Developmental and epileptic encephalopathy, 14

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 26, 2016

- -

Autosomal dominant nocturnal frontal lobe epilepsy 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over