rs150993414
Positions:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4BP6BS2
The NM_001112741.2(KCNC1):c.709C>T(p.Arg237Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,614,112 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000040 ( 0 hom. )
Consequence
KCNC1
NM_001112741.2 missense
NM_001112741.2 missense
Scores
10
9
Clinical Significance
Conservation
PhyloP100: 1.45
Genes affected
KCNC1 (HGNC:6233): (potassium voltage-gated channel subfamily C member 1) This gene encodes a member of a family of integral membrane proteins that mediate the voltage-dependent potassium ion permeability of excitable membranes. Alternative splicing is thought to result in two transcript variants encoding isoforms that differ at their C-termini. These isoforms have had conflicting names in the literature: the longer isoform has been called both "b" and "alpha", while the shorter isoform has been called both "a" and "beta" (PMIDs 1432046, 12091563). [provided by RefSeq, Oct 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), KCNC1. . Gene score misZ 4.5189 (greater than the threshold 3.09). Trascript score misZ 5.1707 (greater than threshold 3.09). GenCC has associacion of gene with progressive myoclonic epilepsy type 7, progressive myoclonus epilepsy, complex neurodevelopmental disorder.
BP4
Computational evidence support a benign effect (MetaRNN=0.35825133).
BP6
Variant 11-17771803-C-T is Benign according to our data. Variant chr11-17771803-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 578002.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BS2
High AC in GnomAdExome4 at 59 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNC1 | NM_001112741.2 | c.709C>T | p.Arg237Trp | missense_variant | 2/4 | ENST00000265969.8 | NP_001106212.1 | |
KCNC1 | NM_004976.4 | c.709C>T | p.Arg237Trp | missense_variant | 2/2 | NP_004967.1 | ||
KCNC1 | XM_047426916.1 | c.709C>T | p.Arg237Trp | missense_variant | 2/4 | XP_047282872.1 | ||
KCNC1 | XR_930866.3 | n.1931C>T | non_coding_transcript_exon_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNC1 | ENST00000265969.8 | c.709C>T | p.Arg237Trp | missense_variant | 2/4 | 5 | NM_001112741.2 | ENSP00000265969 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152230Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000596 AC: 15AN: 251486Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135918
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GnomAD4 exome AF: 0.0000404 AC: 59AN: 1461882Hom.: 0 Cov.: 31 AF XY: 0.0000358 AC XY: 26AN XY: 727244
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152230Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74376
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Progressive myoclonic epilepsy type 7 Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 21, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 12, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
D;T
Sift4G
Uncertain
D;D
Polyphen
P;.
Vest4
MVP
MPC
2.3
ClinPred
T
GERP RS
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