19-50329060-G-C
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2
The NM_004977.3(KCNC3):c.23C>G(p.Ser8Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,311,688 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S8L) has been classified as Uncertain significance.
Frequency
Consequence
NM_004977.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNC3 | NM_004977.3 | c.23C>G | p.Ser8Trp | missense_variant | 1/5 | ENST00000477616.2 | |
KCNC3 | NM_001372305.1 | c.-206C>G | 5_prime_UTR_variant | 1/5 | |||
KCNC3 | NR_110912.2 | n.68+4409C>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNC3 | ENST00000477616.2 | c.23C>G | p.Ser8Trp | missense_variant | 1/5 | 1 | NM_004977.3 | ||
KCNC3 | ENST00000670667.1 | c.23C>G | p.Ser8Trp | missense_variant | 1/4 | P3 | |||
KCNC3 | ENST00000376959.6 | c.23C>G | p.Ser8Trp | missense_variant | 1/5 | 5 | A2 | ||
KCNC3 | ENST00000474951.1 | c.-75+4409C>G | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000215 AC: 30AN: 139268Hom.: 1 Cov.: 22
GnomAD3 exomes AF: 0.0000983 AC: 6AN: 61032Hom.: 0 AF XY: 0.0000838 AC XY: 3AN XY: 35816
GnomAD4 exome AF: 0.000121 AC: 142AN: 1172302Hom.: 1 Cov.: 20 AF XY: 0.000101 AC XY: 58AN XY: 574682
GnomAD4 genome ? AF: 0.000215 AC: 30AN: 139386Hom.: 1 Cov.: 22 AF XY: 0.000104 AC XY: 7AN XY: 67494
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 19, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 26, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | KCNC3: PP2, PP3, BS1 - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 12, 2022 | The c.23C>G (p.S8W) alteration is located in exon 1 (coding exon 1) of the KCNC3 gene. This alteration results from a C to G substitution at nucleotide position 23, causing the serine (S) at amino acid position 8 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 14, 2017 | - - |
KCNC3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 23, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at