19-50320289-A-G
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_004977.3(KCNC3):c.2231T>C(p.Leu744Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 16)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
KCNC3
NM_004977.3 missense
NM_004977.3 missense
Scores
2
7
10
Clinical Significance
Conservation
PhyloP100: 0.462
Publications
0 publications found
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]
KCNC3 Gene-Disease associations (from GenCC):
- spinocerebellar ataxia type 13Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.21747905).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNC3 | NM_004977.3 | c.2231T>C | p.Leu744Ser | missense_variant | Exon 4 of 5 | ENST00000477616.2 | NP_004968.2 | |
KCNC3 | NM_001372305.1 | c.2003T>C | p.Leu668Ser | missense_variant | Exon 4 of 5 | NP_001359234.1 | ||
KCNC3 | NR_110912.2 | n.260+304T>C | intron_variant | Intron 2 of 3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNC3 | ENST00000477616.2 | c.2231T>C | p.Leu744Ser | missense_variant | Exon 4 of 5 | 1 | NM_004977.3 | ENSP00000434241.1 | ||
KCNC3 | ENST00000670667.1 | c.2170+304T>C | intron_variant | Intron 3 of 3 | ENSP00000499301.1 | |||||
KCNC3 | ENST00000376959.6 | c.2170+304T>C | intron_variant | Intron 3 of 4 | 5 | ENSP00000366158.2 | ||||
KCNC3 | ENST00000474951.1 | c.118+304T>C | intron_variant | Intron 2 of 3 | 2 | ENSP00000432438.1 |
Frequencies
GnomAD3 genomes Cov.: 16
GnomAD3 genomes
Cov.:
16
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 793994Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0AN XY: 383866
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
793994
Hom.:
Cov.:
13
AF XY:
AC XY:
0
AN XY:
383866
African (AFR)
AF:
AC:
0
AN:
18702
American (AMR)
AF:
AC:
0
AN:
12752
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
11286
East Asian (EAS)
AF:
AC:
0
AN:
19328
South Asian (SAS)
AF:
AC:
0
AN:
39014
European-Finnish (FIN)
AF:
AC:
0
AN:
21796
Middle Eastern (MID)
AF:
AC:
0
AN:
2560
European-Non Finnish (NFE)
AF:
AC:
0
AN:
636286
Other (OTH)
AF:
AC:
0
AN:
32270
GnomAD4 genome Cov.: 16
GnomAD4 genome
Cov.:
16
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Spinocerebellar ataxia type 13 Uncertain:1
Aug 15, 2024
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
ACMG classification criteria: PM2 supporting, BP4 supporting -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Uncertain
T
MutationAssessor
Benign
N
PhyloP100
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
T
Polyphen
P
Vest4
MutPred
Gain of glycosylation at L744 (P = 0.0049);
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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