Variant rs1060503698 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020822.3(KCNT1):c.199C>G(p.Arg67Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000749 in 1,335,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

KCNT1
NM_020822.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.628

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24297827).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KCNT1	NM_020822.3 linkuse as main transcript	c.199C>G	p.Arg67Gly	missense_variant	2/31	ENST00000371757.7	NP_065873.2
KCNT1	XM_011518878.4 linkuse as main transcript	c.334C>G	p.Arg112Gly	missense_variant	2/31		XP_011517180.1
KCNT1	XM_011518879.4 linkuse as main transcript	c.334C>G	p.Arg112Gly	missense_variant	2/31		XP_011517181.1
KCNT1	NM_001272003.2 linkuse as main transcript	c.110+12297C>G		intron_variant			NP_001258932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNT1	ENST00000371757.7 linkuse as main transcript	c.199C>G	p.Arg67Gly	missense_variant	2/31	1	NM_020822.3	ENSP00000360822	A2	Q5JUK3-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000551

AC:

AN:

181606

Hom.:

AF XY:

0.00000980

AC XY:

AN XY:

102082

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000412

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.49e-7

AC:

AN:

1335940

Hom.:

Cov.:

AF XY:

0.00000150

AC XY:

AN XY:

664822

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.073

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.070

LIST_S2

Uncertain

0.97

D;D;D;D;D

M_CAP

Pathogenic

0.40

MetaRNN

Benign

0.24

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-2.8

.;D;D;N;.

REVEL

Benign

0.18

Sift

Uncertain

0.029

.;D;T;D;.

Sift4G

Uncertain

0.032

D;D;T;T;D

Vest4

0.57

MutPred

0.33

Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);.;.;.;

MVP

0.38

MPC

1.6

ClinPred

0.68

GERP RS

2.6

gMVP

0.61

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over