rs72548727

Variant names:

• chr1-111780417-ATTT-A
• rs72548727
• NM_001378969.1:c.1372-106_1372-104delAAA

Your query was ambiguous. Multiple possible variants found:

• chr1-111780417-ATTT-A
• chr1-111780417-ATTT-AT
• chr1-111780417-ATTT-ATT
• chr1-111780417-ATTT-ATTTT
• chr1-111780417-ATTT-ATTTTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001378969.1(KCND3):​c.1372-106_1372-104delAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,171,638 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: KCND3 NM_001378969.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.882
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 11 AD gene.

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.1372-106_1372-104delAAA		intron	N/A	NP_001365898.1
	KCND3	NM_004980.5		c.1372-106_1372-104delAAA		intron	N/A	NP_004971.2
	KCND3	NM_001378970.1		c.1372-106_1372-104delAAA		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.1372-106_1372-104delAAA		intron	N/A	ENSP00000306923.4
	KCND3	ENST00000315987.6	TSL:1	c.1372-106_1372-104delAAA		intron	N/A	ENSP00000319591.2
	KCND3	ENST00000369697.5	TSL:1	c.1372-106_1372-104delAAA		intron	N/A	ENSP00000358711.1

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151632 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000108 AC: 11 AN: 1019888 Hom.: 0 AF XY: 0.0000116 AC XY: 6 AN XY: 518646

African (AFR) AF: 0.00 AC: 0 AN: 23666

American (AMR) AF: 0.00 AC: 0 AN: 34104

Ashkenazi Jewish (ASJ) AF: 0.000132 AC: 3 AN: 22642

East Asian (EAS) AF: 0.000237 AC: 8 AN: 33770

South Asian (SAS) AF: 0.00 AC: 0 AN: 70764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4350

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 737454

Other (OTH) AF: 0.00 AC: 0 AN: 44946

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151750 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 74160

African (AFR) AF: 0.00 AC: 0 AN: 41404

American (AMR) AF: 0.00 AC: 0 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.000582 AC: 3 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67868

Other (OTH) AF: 0.00 AC: 0 AN: 2100

Alfa AF: 0.00 Hom.: 2

Bravo AF: 0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.88

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: rs72548727; hg19: chr1-112323039;