X-48967086-C-T

Variant names:

• chrX-48967086-C-T
• rs782403572
• NM_004979.6:c.1142G>A

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.1142G>A​(p.Ser381Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000908 in 110,140 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000091 (0 hom., 0 hem., cov: 21)
• Consequence: KCND1 NM_004979.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.398
• 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=0.1840513).

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.1142G>A	p.Ser381Asn	missense	Exon 2 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.1142G>A	p.Ser381Asn	missense	Exon 2 of 6	ENSP00000218176.3	Q9NSA2-1
	KCND1	ENST00000935975.1		c.1142G>A	p.Ser381Asn	missense	Exon 2 of 6	ENSP00000606034.1
	KCND1	ENST00000935976.1		c.1142G>A	p.Ser381Asn	missense	Exon 2 of 6	ENSP00000606035.1

Frequencies

GnomAD3 genomes AF: 0.00000908 AC: 1 AN: 110086 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000190

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000548 AC: 1 AN: 182602 AF XY: 0.00

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: 0.0000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000908 AC: 1 AN: 110140 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 32376

African (AFR) AF: 0.00 AC: 0 AN: 30266

American (AMR) AF: 0.00 AC: 0 AN: 10296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2634

East Asian (EAS) AF: 0.00 AC: 0 AN: 3429

South Asian (SAS) AF: 0.00 AC: 0 AN: 2562

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5816

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 214

European-Non Finnish (NFE) AF: 0.0000190 AC: 1 AN: 52744

Other (OTH) AF: 0.00 AC: 0 AN: 1502

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.18	T
MetaSVM	Uncertain	0.34	D
MutationAssessor	Benign	0.84	L
PhyloP100		0.40
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.23
Sift	Benign	0.16	T
Sift4G	Benign	0.26	T
Polyphen		0.0010	B
Vest4		0.068
MutPred		0.33		Loss of glycosylation at S381 (P = 0.0234)
MVP		0.80
MPC		0.78
ClinPred		0.28	T
GERP RS		4.8
PromoterAI		0.027	Neutral
Varity_R		0.24
gMVP		0.88
Mutation Taster		=72/28	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: rs782403572; hg19: chrX-48823493;