16-1209405-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_021098.3(CACNA1H):c.3737C>T(p.Ser1246Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000764 in 1,597,532 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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. S1246P) has been classified as Likely benign.
Frequency
Consequence
NM_021098.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1H | NM_021098.3 | c.3737C>T | p.Ser1246Leu | missense_variant | 17/35 | ENST00000348261.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1H | ENST00000348261.11 | c.3737C>T | p.Ser1246Leu | missense_variant | 17/35 | 1 | NM_021098.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152216Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000868 AC: 20AN: 230302Hom.: 0 AF XY: 0.0000785 AC XY: 10AN XY: 127382
GnomAD4 exome AF: 0.0000768 AC: 111AN: 1445198Hom.: 1 Cov.: 32 AF XY: 0.0000737 AC XY: 53AN XY: 719304
GnomAD4 genome AF: 0.0000722 AC: 11AN: 152334Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74486
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2018 | - - |
Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at