rs749790557
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4_StrongBP6BS1BS2
The NM_001112741.2(KCNC1):c.494C>T(p.Pro165Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000069 in 1,593,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001112741.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNC1 | NM_001112741.2 | c.494C>T | p.Pro165Leu | missense_variant | 1/4 | ENST00000265969.8 | |
KCNC1 | NM_004976.4 | c.494C>T | p.Pro165Leu | missense_variant | 1/2 | ||
KCNC1 | XM_047426916.1 | c.494C>T | p.Pro165Leu | missense_variant | 1/4 | ||
KCNC1 | XR_930866.3 | n.1716C>T | non_coding_transcript_exon_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNC1 | ENST00000265969.8 | c.494C>T | p.Pro165Leu | missense_variant | 1/4 | 5 | NM_001112741.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000335 AC: 7AN: 209144Hom.: 0 AF XY: 0.0000257 AC XY: 3AN XY: 116806
GnomAD4 exome AF: 0.00000694 AC: 10AN: 1441512Hom.: 0 Cov.: 32 AF XY: 0.00000697 AC XY: 5AN XY: 716944
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74372
ClinVar
Submissions by phenotype
Progressive myoclonic epilepsy type 7 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 25, 2023 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 165 of the KCNC1 protein (p.Pro165Leu). This variant is present in population databases (rs749790557, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of KCNC1-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 475356). 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. 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. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 26, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at