rs749270474
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2
The NM_001112741.2(KCNC1):āc.1673C>Gā(p.Pro558Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000084 in 1,548,256 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 (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P558L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001112741.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNC1 | NM_001112741.2 | c.1673C>G | p.Pro558Arg | missense_variant | 3/4 | ENST00000265969.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNC1 | ENST00000265969.8 | c.1673C>G | p.Pro558Arg | missense_variant | 3/4 | 5 | NM_001112741.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152192Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000133 AC: 2AN: 150700Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 79994
GnomAD4 exome AF: 0.00000501 AC: 7AN: 1396064Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1AN XY: 688506
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152192Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74338
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 30, 2021 | The c.1673C>G (p.P558R) alteration is located in exon 3 (coding exon 3) of the KCNC1 gene. This alteration results from a C to G substitution at nucleotide position 1673, causing the proline (P) at amino acid position 558 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Progressive myoclonic epilepsy type 7 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 03, 2023 | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 558 of the KCNC1 protein (p.Pro558Arg). This variant is present in population databases (rs749270474, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with KCNC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 567831). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KCNC1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Apr 21, 2023 | PP2 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at