19-50323757-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3PP5BS2
The NM_004977.3(KCNC3):c.1196C>T(p.Ser399Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S399S) has been classified as Likely benign.
Frequency
Consequence
NM_004977.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNC3 | NM_004977.3 | c.1196C>T | p.Ser399Leu | missense_variant | 2/5 | ENST00000477616.2 | |
KCNC3 | NM_001372305.1 | c.968C>T | p.Ser323Leu | missense_variant | 2/5 | ||
KCNC3 | NR_110912.2 | n.69-2973C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNC3 | ENST00000477616.2 | c.1196C>T | p.Ser399Leu | missense_variant | 2/5 | 1 | NM_004977.3 | ||
KCNC3 | ENST00000670667.1 | c.1196C>T | p.Ser399Leu | missense_variant | 2/4 | P3 | |||
KCNC3 | ENST00000376959.6 | c.1196C>T | p.Ser399Leu | missense_variant | 2/5 | 5 | A2 | ||
KCNC3 | ENST00000474951.1 | c.-74-2973C>T | intron_variant | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461874Hom.: 0 Cov.: 34 AF XY: 0.00000550 AC XY: 4AN XY: 727238
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 06, 2017 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Mar 24, 2020 | Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 01, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at