chrX-49205151-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001256789.3(CACNA1F):c.5887G>A(p.Val1963Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000732 in 1,092,959 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001256789.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1F | NM_001256789.3 | c.5887G>A | p.Val1963Ile | missense_variant | 48/48 | ENST00000323022.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1F | ENST00000323022.10 | c.5887G>A | p.Val1963Ile | missense_variant | 48/48 | 1 | NM_001256789.3 | ||
CACNA1F | ENST00000376265.2 | c.5920G>A | p.Val1974Ile | missense_variant | 48/48 | 1 | P1 | ||
CACNA1F | ENST00000376251.5 | c.5725G>A | p.Val1909Ile | missense_variant | 48/48 | 1 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD3 exomes AF: 0.0000111 AC: 2AN: 180966Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 65832
GnomAD4 exome AF: 0.00000732 AC: 8AN: 1092959Hom.: 0 Cov.: 29 AF XY: 0.0000112 AC XY: 4AN XY: 358689
GnomAD4 genome Cov.: 22
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 03, 2023 | 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 output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with CACNA1F-related conditions. This variant is present in population databases (rs782793473, gnomAD 0.01%). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1974 of the CACNA1F protein (p.Val1974Ile). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at