rs869312682

chr9-135714602-C-Gchr9-135714602-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020822.3(KCNT1):c.136C>G(p.Leu46Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L46F) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNT1 NM_020822.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06078306).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNT1	NM_020822.3	c.136C>G	p.Leu46Val	missense_variant	2/31	ENST00000371757.7
KCNT1	XM_011518878.4	c.271C>G	p.Leu91Val	missense_variant	2/31
KCNT1	XM_011518879.4	c.271C>G	p.Leu91Val	missense_variant	2/31
KCNT1	NM_001272003.2	c.110+12234C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNT1	ENST00000371757.7	c.136C>G	p.Leu46Val	missense_variant	2/31	1	NM_020822.3	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1281190 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 637266

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
Cadd	Benign	8.7
Dann	Benign	0.89
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.36	T;T
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.061	T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	D;D;N;N
PrimateAI	Uncertain	0.73	T
Sift4G	Benign	0.17	T;T
Vest4		0.086
MutPred		0.14		Loss of solvent accessibility (P = 0.089);Loss of solvent accessibility (P = 0.089);
MVP		0.16
MPC		0.64
ClinPred		0.19	T
GERP RS		2.7
gMVP		0.080

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

Other links and lift over

dbSNP: rs869312682; hg19: chr9-138606448;