rs775725087
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2
The NM_001112741.2(KCNC1):āc.1627T>Cā(p.Tyr543His) variant causes a missense change. The variant allele was found at a frequency of 0.0000229 in 1,399,244 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 ). Synonymous variant affecting the same amino acid position (i.e. Y543Y) has been classified as Benign.
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.1627T>C | p.Tyr543His | missense_variant | 3/4 | ENST00000265969.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNC1 | ENST00000265969.8 | c.1627T>C | p.Tyr543His | missense_variant | 3/4 | 5 | NM_001112741.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000650 AC: 1AN: 153842Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 81636
GnomAD4 exome AF: 0.0000229 AC: 32AN: 1399244Hom.: 0 Cov.: 31 AF XY: 0.0000203 AC XY: 14AN XY: 690156
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Progressive myoclonic epilepsy type 7 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 02, 2022 | 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. 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 not expected to disrupt KCNC1 protein function. ClinVar contains an entry for this variant (Variation ID: 542105). This variant has not been reported in the literature in individuals affected with KCNC1-related conditions. This variant is present in population databases (rs775725087, gnomAD 0.002%). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 543 of the KCNC1 protein (p.Tyr543His). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at