rs1554976231
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM5
The NM_031418.4(ANO3):āc.1795G>Cā(p.Ala599Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A599D) has been classified as Likely pathogenic.
Frequency
Consequence
NM_031418.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANO3 | NM_031418.4 | c.1795G>C | p.Ala599Pro | missense_variant | 17/27 | ENST00000256737.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANO3 | ENST00000256737.8 | c.1795G>C | p.Ala599Pro | missense_variant | 17/27 | 1 | NM_031418.4 | P3 | |
ANO3 | ENST00000672621.1 | c.1978G>C | p.Ala660Pro | missense_variant | 18/28 | ||||
ANO3 | ENST00000525139.5 | c.1747G>C | p.Ala583Pro | missense_variant | 17/27 | 5 | |||
ANO3 | ENST00000531568.1 | c.1357G>C | p.Ala453Pro | missense_variant | 14/24 | 2 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461792Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727194
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Dystonic disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 15, 2017 | This sequence change replaces alanine with proline at codon 599 of the ANO3 protein (p.Ala599Pro). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ANO3-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at