NM_001378969.1:c.1107-96791A>C

Variant names:

• chr1-111883897-T-G
• rs11102353
• NM_001378969.1:c.1107-96791A>C

Variant summary

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

The NM_001378969.1(KCND3):​c.1107-96791A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 152,110 control chromosomes in the GnomAD database, including 12,064 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 0.39 (12064 hom., cov: 32)
• Consequence: KCND3 NM_001378969.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.465
• Publications: 7 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.447 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.1107-96791A>C		intron	N/A	NP_001365898.1
	KCND3	NM_004980.5		c.1107-96791A>C		intron	N/A	NP_004971.2
	KCND3	NM_001378970.1		c.1107-96791A>C		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.1107-96791A>C		intron	N/A	ENSP00000306923.4
	KCND3	ENST00000315987.6	TSL:1	c.1107-96791A>C		intron	N/A	ENSP00000319591.2
	KCND3	ENST00000369697.5	TSL:1	c.1107-96791A>C		intron	N/A	ENSP00000358711.1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59355 AN: 151992 Hom.: 12061 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.390 AC: 59360 AN: 152110 Hom.: 12064 Cov.: 32 AF XY: 0.393 AC XY: 29230 AN XY: 74338

African (AFR) AF: 0.280 AC: 11595 AN: 41480

American (AMR) AF: 0.454 AC: 6945 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1845 AN: 3472

East Asian (EAS) AF: 0.392 AC: 2032 AN: 5178

South Asian (SAS) AF: 0.463 AC: 2235 AN: 4828

European-Finnish (FIN) AF: 0.405 AC: 4280 AN: 10568

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28856 AN: 67982

Other (OTH) AF: 0.429 AC: 907 AN: 2112

Alfa AF: 0.412 Hom.: 15807

Bravo AF: 0.389

Asia WGS AF: 0.403 AC: 1403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.7
DANN	Benign	0.81
PhyloP100		0.47
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: rs11102353; hg19: chr1-112426519;