rs781923856
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP5
The NM_001256789.3(CACNA1F):c.1606G>A(p.Ala536Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000104 in 1,056,120 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A536A) has been classified as Likely benign.
Frequency
Consequence
NM_001256789.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1F | NM_001256789.3 | c.1606G>A | p.Ala536Thr | missense_variant | 13/48 | ENST00000323022.10 | |
CACNA1F | NM_005183.4 | c.1639G>A | p.Ala547Thr | missense_variant | 13/48 | ||
CACNA1F | NM_001256790.3 | c.1444G>A | p.Ala482Thr | missense_variant | 13/48 | ||
CACNA1F | XM_011543983.3 | c.1444G>A | p.Ala482Thr | missense_variant | 13/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1F | ENST00000323022.10 | c.1606G>A | p.Ala536Thr | missense_variant | 13/48 | 1 | NM_001256789.3 | ||
CACNA1F | ENST00000376265.2 | c.1639G>A | p.Ala547Thr | missense_variant | 13/48 | 1 | P1 | ||
CACNA1F | ENST00000376251.5 | c.1444G>A | p.Ala482Thr | missense_variant | 13/48 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 exomes AF: 0.0000170 AC: 2AN: 117830Hom.: 0 AF XY: 0.0000244 AC XY: 1AN XY: 40958
GnomAD4 exome AF: 0.0000104 AC: 11AN: 1056120Hom.: 0 Cov.: 31 AF XY: 0.0000116 AC XY: 4AN XY: 345238
GnomAD4 genome ? Cov.: 23
ClinVar
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | May 20, 2015 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 22, 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CACNA1F protein function. ClinVar contains an entry for this variant (Variation ID: 520685). This variant has not been reported in the literature in individuals affected with CACNA1F-related conditions. This variant is present in population databases (rs781923856, gnomAD 0.007%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 547 of the CACNA1F protein (p.Ala547Thr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at