chr9-135702305-A-G

Position:

• chr9-135702305-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020822.3(KCNT1):​c.47A>G​(p.Glu16Gly) 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. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KCNT1 NM_020822.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.734

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]

SOHLH1 (HGNC:):

ACMG classification

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=0.08613014).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNT1	NM_020822.3	c.47A>G	p.Glu16Gly	missense_variant	1/31	ENST00000371757.7	NP_065873.2
KCNT1	NM_001272003.2	c.47A>G	p.Glu16Gly	missense_variant	1/31		NP_001258932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNT1	ENST00000371757.7	c.47A>G	p.Glu16Gly	missense_variant	1/31	1	NM_020822.3	ENSP00000360822.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.76
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.40	T;T;T
M_CAP	Pathogenic	0.34	D
MetaRNN	Benign	0.086	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.1	N;.;N
REVEL	Benign	0.0060
Sift	Benign	0.15	T;.;T
Sift4G	Pathogenic	0.0	D;T;D
Vest4		0.062
MutPred		0.31		Loss of solvent accessibility (P = 0.0224);Loss of solvent accessibility (P = 0.0224);Loss of solvent accessibility (P = 0.0224);
MVP		0.048
MPC		0.74
ClinPred		0.036	T
GERP RS		-1.6
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-138594151;