NM_001378969.1:c.1106+51470G>A

Variant names:

• chr1-111930151-C-T
• rs1443928
• NM_001378969.1:c.1106+51470G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378969.1(KCND3):​c.1106+51470G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 151,010 control chromosomes in the GnomAD database, including 11,014 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 0.35 (11014 hom., cov: 32)
• Consequence: KCND3 NM_001378969.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163
• Publications: 3 publications found

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]

KCND3 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: G2P
• spinocerebellar ataxia type 19/22

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, Ambry Genetics
• Brugada syndrome 9

  Inheritance: AD Classification: LIMITED Submitted by: Genomics England PanelApp
• Brugada syndrome 1

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378969.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCND3	NM_001378969.1	MANE Select	c.1106+51470G>A		intron	N/A	NP_001365898.1
	KCND3	NM_004980.5		c.1106+51470G>A		intron	N/A	NP_004971.2
	KCND3	NM_001378970.1		c.1106+51470G>A		intron	N/A	NP_001365899.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCND3	ENST00000302127.5	TSL:5 MANE Select	c.1106+51470G>A		intron	N/A	ENSP00000306923.4
	KCND3	ENST00000315987.6	TSL:1	c.1106+51470G>A		intron	N/A	ENSP00000319591.2
	KCND3	ENST00000369697.5	TSL:1	c.1106+51470G>A		intron	N/A	ENSP00000358711.1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53261 AN: 150928 Hom.: 11015 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.353 AC: 53270 AN: 151010 Hom.: 11014 Cov.: 32 AF XY: 0.352 AC XY: 25966 AN XY: 73734

African (AFR) AF: 0.127 AC: 5223 AN: 41134

American (AMR) AF: 0.411 AC: 6253 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1516 AN: 3466

East Asian (EAS) AF: 0.466 AC: 2394 AN: 5140

South Asian (SAS) AF: 0.337 AC: 1608 AN: 4778

European-Finnish (FIN) AF: 0.410 AC: 4183 AN: 10200

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.455 AC: 30819 AN: 67780

Other (OTH) AF: 0.380 AC: 793 AN: 2086

Alfa AF: 0.398 Hom.: 8597

Bravo AF: 0.342

Asia WGS AF: 0.351 AC: 1220 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.75
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1443928; hg19: chr1-112472773;