chr19-50320313-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_004977.3(KCNC3):c.2207G>A(p.Arg736His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNC3 | NM_004977.3 | c.2207G>A | p.Arg736His | missense_variant | Exon 4 of 5 | ENST00000477616.2 | NP_004968.2 | |
KCNC3 | NM_001372305.1 | c.1979G>A | p.Arg660His | missense_variant | Exon 4 of 5 | NP_001359234.1 | ||
KCNC3 | NR_110912.2 | n.260+280G>A | intron_variant | Intron 2 of 3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNC3 | ENST00000477616.2 | c.2207G>A | p.Arg736His | missense_variant | Exon 4 of 5 | 1 | NM_004977.3 | ENSP00000434241.1 | ||
KCNC3 | ENST00000670667.1 | c.2170+280G>A | intron_variant | Intron 3 of 3 | ENSP00000499301.1 | |||||
KCNC3 | ENST00000376959.6 | c.2170+280G>A | intron_variant | Intron 3 of 4 | 5 | ENSP00000366158.2 | ||||
KCNC3 | ENST00000474951.1 | c.118+280G>A | intron_variant | Intron 2 of 3 | 2 | ENSP00000432438.1 |
Frequencies
GnomAD3 genomes AF: 0.00000905 AC: 1AN: 110488Hom.: 0 Cov.: 16
GnomAD3 exomes AF: 0.0000585 AC: 3AN: 51290Hom.: 0 AF XY: 0.0000381 AC XY: 1AN XY: 26248
GnomAD4 exome AF: 0.00000587 AC: 4AN: 681968Hom.: 0 Cov.: 10 AF XY: 0.00000295 AC XY: 1AN XY: 339552
GnomAD4 genome AF: 0.00000905 AC: 1AN: 110504Hom.: 0 Cov.: 16 AF XY: 0.0000196 AC XY: 1AN XY: 50952
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: KCNC3 c.2207G>A (p.Arg736His) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 5.8e-05 in 51290 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2207G>A in individuals affected with Spinocerebellar Ataxia Type 13 and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at