chr19-50320620-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_004977.3(KCNC3):c.2143C>T(p.Pro715Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,612,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
KCNC3
NM_004977.3 missense
NM_004977.3 missense
Scores
2
5
11
Clinical Significance
Conservation
PhyloP100: 2.52
Genes affected
KCNC3 (HGNC:6235): (potassium voltage-gated channel subfamily C member 3) The Shaker gene family of Drosophila encodes components of voltage-gated potassium channels and is comprised of four subfamilies. Based on sequence similarity, this gene is similar to one of these subfamilies, namely the Shaw subfamily. The protein encoded by this gene belongs to the delayed rectifier class of channel proteins and is an integral membrane protein that mediates the voltage-dependent potassium ion permeability of excitable membranes. Alternate splicing results in several transcript variants. [provided by RefSeq, Mar 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.11774993).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNC3 | NM_004977.3 | c.2143C>T | p.Pro715Ser | missense_variant | 3/5 | ENST00000477616.2 | |
KCNC3 | NM_001372305.1 | c.1915C>T | p.Pro639Ser | missense_variant | 3/5 | ||
KCNC3 | NR_110912.2 | n.233C>T | non_coding_transcript_exon_variant | 2/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNC3 | ENST00000477616.2 | c.2143C>T | p.Pro715Ser | missense_variant | 3/5 | 1 | NM_004977.3 | ||
KCNC3 | ENST00000670667.1 | c.2143C>T | p.Pro715Ser | missense_variant | 3/4 | P3 | |||
KCNC3 | ENST00000376959.6 | c.2143C>T | p.Pro715Ser | missense_variant | 3/5 | 5 | A2 | ||
KCNC3 | ENST00000474951.1 | c.91C>T | p.Pro31Ser | missense_variant | 2/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152006Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249392Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135112
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1460546Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 726556
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152006Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1AN XY: 74220
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Spinocerebellar ataxia type 13 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Apr 13, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;N;N;N
PrimateAI
Pathogenic
T
PROVEAN
Benign
N;D;N
REVEL
Uncertain
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
B;.;B
Vest4
MutPred
Gain of phosphorylation at P715 (P = 0.0377);.;Gain of phosphorylation at P715 (P = 0.0377);
MVP
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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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