rs12044963

Positions:

• chr1-111849738-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378969.1(KCND3):​c.1107-62632C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,186 control chromosomes in the GnomAD database, including 1,364 homozygotes. 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: 𝑓 0.11 (1364 hom., cov: 32)
• Consequence: KCND3 NM_001378969.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135

Genes affected

KCND3 (HGNC:6239): (potassium voltage-gated channel subfamily D member 3) Voltage-gated potassium (Kv) 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. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shal-related subfamily, members of which form voltage-activated A-type potassium ion channels and are prominent in the repolarization phase of the action potential. This member includes two isoforms with different sizes, which are encoded by alternatively spliced transcript variants of this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCND3	NM_001378969.1	c.1107-62632C>A		intron_variant		ENST00000302127.5	NP_001365898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCND3	ENST00000302127.5	c.1107-62632C>A		intron_variant		5	NM_001378969.1	ENSP00000306923	P3

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16775 AN: 152068 Hom.: 1361 Cov.: 32

Gnomad AFR AF: 0.0588

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.0795

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0876

Gnomad OTH AF: 0.118

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.110 AC: 16788 AN: 152186 Hom.: 1364 Cov.: 32 AF XY: 0.119 AC XY: 8857 AN XY: 74384

Gnomad4 AFR AF: 0.0587

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.0795

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.0876

Gnomad4 OTH AF: 0.121

Alfa AF: 0.0939 Hom.: 1736

Bravo AF: 0.111

Asia WGS AF: 0.298 AC: 1033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.60

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: rs12044963; hg19: chr1-112392360;