rs692982

Variant names:

• chr1-111837912-C-G
• rs692982
• NM_001378969.1:c.1107-50806G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-111837912-C-G
• chr1-111837912-C-T

Variant summary

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

The NM_001378969.1(KCND3):​c.1107-50806G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,952 control chromosomes in the GnomAD database, including 9,368 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 0.34 (9368 hom., cov: 32)
• Consequence: KCND3 NM_001378969.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCND3	NM_001378969.1	c.1107-50806G>C		intron_variant	Intron 2 of 7	ENST00000302127.5	NP_001365898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCND3	ENST00000302127.5	c.1107-50806G>C		intron_variant	Intron 2 of 7	5	NM_001378969.1	ENSP00000306923.4
KCND3	ENST00000315987.6	c.1107-50806G>C		intron_variant	Intron 2 of 7	1		ENSP00000319591.2
KCND3	ENST00000369697.5	c.1107-50806G>C		intron_variant	Intron 1 of 5	1		ENSP00000358711.1
KCND3	ENST00000703641.1	n.5542G>C		non_coding_transcript_exon_variant	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52152 AN: 151834 Hom.: 9353 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.0947

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.344 AC: 52210 AN: 151952 Hom.: 9368 Cov.: 32 AF XY: 0.348 AC XY: 25814 AN XY: 74244

African (AFR) AF: 0.363 AC: 15018 AN: 41400

American (AMR) AF: 0.356 AC: 5444 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1048 AN: 3468

East Asian (EAS) AF: 0.648 AC: 3348 AN: 5168

South Asian (SAS) AF: 0.428 AC: 2059 AN: 4808

European-Finnish (FIN) AF: 0.354 AC: 3731 AN: 10538

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20663 AN: 67982

Other (OTH) AF: 0.336 AC: 711 AN: 2114

Alfa AF: 0.321 Hom.: 981

Bravo AF: 0.344

Asia WGS AF: 0.526 AC: 1827 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.1
DANN	Benign	0.71
PhyloP100		-0.050
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: rs692982; hg19: chr1-112380534;