NM_004979.6:c.1057A>C

Variant names:

• chrX-48969215-T-G
• rs143686945
• NM_004979.6:c.1057A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004979.6(KCND1):​c.1057A>C​(p.Lys353Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 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. K353E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: KCND1 NM_004979.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11300579).

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.1057A>C	p.Lys353Gln	missense	Exon 1 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.1057A>C	p.Lys353Gln	missense	Exon 1 of 6	ENSP00000218176.3	Q9NSA2-1
	KCND1	ENST00000935975.1		c.1057A>C	p.Lys353Gln	missense	Exon 1 of 6	ENSP00000606034.1
	KCND1	ENST00000935976.1		c.1057A>C	p.Lys353Gln	missense	Exon 1 of 6	ENSP00000606035.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	0.0082	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	22
DANN	Benign	0.80
DEOGEN2	Benign	0.35	T
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.11	T
MetaSVM	Uncertain	-0.060	T
MutationAssessor	Benign	-0.23	N
PhyloP100		1.7
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.020	N
REVEL	Uncertain	0.32
Sift	Benign	0.55	T
Sift4G	Benign	0.26	T
Polyphen		0.0030	B
Vest4		0.097
MutPred		0.39		Loss of methylation at K353 (P = 0.0092)
MVP		0.81
MPC		0.90
ClinPred		0.19	T
GERP RS		4.3
Varity_R		0.18
gMVP		0.89
Mutation Taster		=98/2	polymorphism

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: rs143686945; hg19: chrX-48825622;