Genetic Variant KCND1:p.Ile391Val (chrX-48967057-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004979.6(KCND1):c.1171A>G(p.Ile391Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000911 in 109,820 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. 12/21 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.470

Publications

0 publications found

Variant links:

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]

KCND1 links:

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ACMG classification

Classification was made for transcript

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=0.20907825).

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.1171A>G	p.Ile391Val	missense	Exon 2 of 6	NP_004970.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCND1	ENST00000218176.4	TSL:1 MANE Select	c.1171A>G	p.Ile391Val	missense	Exon 2 of 6	ENSP00000218176.3	Q9NSA2-1
KCND1	ENST00000935975.1		c.1171A>G	p.Ile391Val	missense	Exon 2 of 6	ENSP00000606034.1
KCND1	ENST00000935976.1		c.1171A>G	p.Ile391Val	missense	Exon 2 of 6	ENSP00000606035.1

Frequencies

GnomAD3 genomes

AF:

0.00000911

AC:

AN:

109820

Hom.:

Cov.:

show subpopulations

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:

0.00

Gnomad OTH

AF:

0.000682

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000911

AC:

AN:

109820

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32070

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30103

American (AMR)

AF:

0.00

AC:

AN:

10260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2625

East Asian (EAS)

AF:

0.00

AC:

AN:

3431

South Asian (SAS)

AF:

0.00

AC:

AN:

2562

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5784

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52670

Other (OTH)

AF:

0.000682

AC:

AN:

1467

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.38

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.056

MetaRNN

Benign

0.21

MetaSVM

Uncertain

0.28

MutationAssessor

Benign

0.040

PhyloP100

0.47

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.28

REVEL

Benign

0.22

Sift

Benign

0.32

Sift4G

Benign

0.65

Polyphen

0.0030

Vest4

0.30

MutPred

0.47

Loss of ubiquitination at K386 (P = 0.1091)

MVP

0.94

MPC

0.71

ClinPred

0.21

GERP RS

4.5

PromoterAI

0.0076

Neutral

(source)

Varity_R

0.18

gMVP

0.90

Mutation Taster

=87/13

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over