rs369562243

Variant names:

• chr9-135768607-C-A
• NM_020822.3:c.1338-3C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-135768607-C-A
• chr9-135768607-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020822.3(KCNT1):​c.1338-3C>A variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000000715 in 1,397,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: KCNT1 NM_020822.3 splice_region, intron
• Scores: Splicing: ADA: 0.9972
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.83

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNT1	NM_020822.3	c.1338-3C>A		splice_region_variant, intron_variant	Intron 13 of 30	ENST00000371757.7	NP_065873.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNT1	ENST00000371757.7	c.1338-3C>A		splice_region_variant, intron_variant	Intron 13 of 30	1	NM_020822.3	ENSP00000360822.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1397988 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 689576

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000280

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.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Benign	0.96

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.90
SpliceAI score (max)		0.84		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.84		Position offset: 3

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: chr9-138660453;