rs781797726

Variant names:

• chrX-48966169-C-A
• rs781797726
• NM_004979.6:c.1604G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-48966169-C-A
• chrX-48966169-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004979.6(KCND1):​c.1604G>T​(p.Arg535Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000912 in 1,096,108 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R535H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
• Consequence: KCND1 NM_004979.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.15
• Publications: 0 publications found

Genes affected

KCND1 (HGNC:6237): (potassium voltage-gated channel subfamily D member 1) This gene encodes a multipass membrane protein that comprises the pore subunit of the voltage-gated A-type potassium channel, which functions in the repolarization of membrane action potentials. Activity of voltage-gated potassium channels is important in a number of physiological processes, among them the regulation of neurotransmitter release, heart rate, insulin secretion, and smooth muscle contraction. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004979.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCND1	NM_004979.6	MANE Select	c.1604G>T	p.Arg535Leu	missense	Exon 5 of 6	NP_004970.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCND1	ENST00000218176.4	TSL:1 MANE Select	c.1604G>T	p.Arg535Leu	missense	Exon 5 of 6	ENSP00000218176.3	Q9NSA2-1
	KCND1	ENST00000935975.1		c.1616G>T	p.Arg539Leu	missense	Exon 5 of 6	ENSP00000606034.1
	KCND1	ENST00000935976.1		c.1601G>T	p.Arg534Leu	missense	Exon 5 of 6	ENSP00000606035.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.00000562 AC: 1 AN: 178061 AF XY: 0.0000156

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000126

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1096108 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 1 AN XY: 362224

African (AFR) AF: 0.00 AC: 0 AN: 26367

American (AMR) AF: 0.00 AC: 0 AN: 35086

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19250

East Asian (EAS) AF: 0.00 AC: 0 AN: 30188

South Asian (SAS) AF: 0.00 AC: 0 AN: 53814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3408

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841792

Other (OTH) AF: 0.00 AC: 0 AN: 45971

GnomAD4 genome Cov.: 24

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.83	D
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D
M_CAP	Pathogenic	0.35	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Uncertain	0.52	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		5.1
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Pathogenic	0.71
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.028	D
Polyphen		0.99	D
Vest4		0.74
MutPred		0.30		Loss of MoRF binding (P = 0.0521)
MVP		0.89
MPC		0.33
ClinPred		0.96	D
GERP RS		4.5
Varity_R		0.71
gMVP		0.73
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs781797726; hg19: chrX-48822576;