rs1553749683
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000726.5(CACNB4):c.770C>T(p.Thr257Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,456,076 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 Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T257T) has been classified as Likely benign.
Frequency
Consequence
NM_000726.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNB4 | NM_000726.5 | c.770C>T | p.Thr257Met | missense_variant | 10/14 | ENST00000539935.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNB4 | ENST00000539935.7 | c.770C>T | p.Thr257Met | missense_variant | 10/14 | 1 | NM_000726.5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000275 AC: 4AN: 1456076Hom.: 0 Cov.: 28 AF XY: 0.00000414 AC XY: 3AN XY: 724734
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Idiopathic generalized epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 14, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 460001). This variant has not been reported in the literature in individuals affected with CACNB4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 257 of the CACNB4 protein (p.Thr257Met). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at