X-48962741-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004979.6(KCND1):āc.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
NM_004979.6 missense
Scores
6
11
Clinical Significance
Conservation
PhyloP100: 5.00
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]
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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
Ensembl
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD3 genomes
Cov.:
22
GnomAD3 exomes AF: 0.0000111 AC: 2AN: 180146Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 65398
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GnomAD4 exome AF: 0.00000182 AC: 2AN: 1097390Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 362772
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GnomAD4 genome Cov.: 22
GnomAD4 genome
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22
ExAC
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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 submitter | clinical testing | Ambry Genetics | Dec 19, 2022 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
.;L
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;T
Polyphen
0.0040
.;B
Vest4
MutPred
0.33
.;Loss of sheet (P = 3e-04);
MVP
MPC
0.062
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at