X-48962741-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004979.6(KCND1):ā€‹c.1784T>Cā€‹(p.Val595Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,097,390 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. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 22)
Exomes š‘“: 0.0000018 ( 0 hom. 0 hem. )

Consequence

KCND1
NM_004979.6 missense

Scores

6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.00
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14063361).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KCND1NM_004979.6 linkc.1784T>C p.Val595Ala missense_variant 6/6 ENST00000218176.4 NP_004970.3 Q9NSA2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KCND1ENST00000218176.4 linkc.1784T>C p.Val595Ala missense_variant 6/61 NM_004979.6 ENSP00000218176.3 Q9NSA2-1
KCND1ENST00000376477.5 linkc.653T>C p.Val218Ala missense_variant 5/52 ENSP00000365660.1 Q9NSA2-2

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD3 exomes
AF:
0.0000111
AC:
2
AN:
180146
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
65398
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000145
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000182
AC:
2
AN:
1097390
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
362772
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000662
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
22
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 19, 2022The c.1784T>C (p.V595A) alteration is located in exon 6 (coding exon 6) of the KCND1 gene. This alteration results from a T to C substitution at nucleotide position 1784, causing the valine (V) at amino acid position 595 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.094
.;T
FATHMM_MKL
Benign
0.55
D
LIST_S2
Benign
0.66
T;T
M_CAP
Uncertain
0.21
D
MetaRNN
Benign
0.14
T;T
MetaSVM
Uncertain
-0.10
T
MutationAssessor
Benign
0.90
.;L
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-0.57
N;N
REVEL
Benign
0.28
Sift
Uncertain
0.0080
D;D
Sift4G
Uncertain
0.033
D;T
Polyphen
0.0040
.;B
Vest4
0.11
MutPred
0.33
.;Loss of sheet (P = 3e-04);
MVP
0.94
MPC
0.062
ClinPred
0.26
T
GERP RS
3.8
Varity_R
0.10
gMVP
0.60

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs782724095; hg19: chrX-48820002; API