rs879253883
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP3_ModeratePP5
The NM_004977.3(KCNC3):c.1283C>T(p.Thr428Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. T428T) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
KCNC3
NM_004977.3 missense
NM_004977.3 missense
Scores
9
8
1
Clinical Significance
Conservation
PhyloP100: 9.81
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_pathogenic. Variant got 7 ACMG points.
PM1
?
In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 3 uncertain in NM_004977.3
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.939
PP5
?
Variant 19-50323670-G-A is Pathogenic according to our data. Variant chr19-50323670-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 245604.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNC3 | NM_004977.3 | c.1283C>T | p.Thr428Ile | missense_variant | 2/5 | ENST00000477616.2 | |
KCNC3 | NM_001372305.1 | c.1055C>T | p.Thr352Ile | missense_variant | 2/5 | ||
KCNC3 | NR_110912.2 | n.69-2886C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNC3 | ENST00000477616.2 | c.1283C>T | p.Thr428Ile | missense_variant | 2/5 | 1 | NM_004977.3 | ||
KCNC3 | ENST00000670667.1 | c.1283C>T | p.Thr428Ile | missense_variant | 2/4 | P3 | |||
KCNC3 | ENST00000376959.6 | c.1283C>T | p.Thr428Ile | missense_variant | 2/5 | 5 | A2 | ||
KCNC3 | ENST00000474951.1 | c.-74-2886C>T | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 34
GnomAD4 exome
Cov.:
34
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Spinocerebellar ataxia type 13 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 20, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Gain of methylation at K426 (P = 0.0531);Gain of methylation at K426 (P = 0.0531);
MVP
ClinPred
D
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