3-43605851-A-G
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1_SupportingPM2PP5_Very_Strong
The NM_018075.5(ANO10):c.2T>C(p.Met1?) variant causes a start lost change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,548 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 Likely pathogenic (★★).
Frequency
Consequence
NM_018075.5 start_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ANO10 | NM_018075.5 | c.2T>C | p.Met1? | start_lost | Exon 2 of 13 | ENST00000292246.8 | NP_060545.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251084Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135734
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461228Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 726924
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152320Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74484
ClinVar
Submissions by phenotype
not provided Pathogenic:2
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The c.2 T>C variant in the ANO10 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. As this variant changes the translation initiator Methionine codon, the resultant protein is described as p.Met1?, using a question mark to signify that it is not known if the loss of Met1 means that all protein translation is completely prevented or if an abnormal protein is produced using an alternate Methionine. The c.2 T>C variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.2 T>C as a pathogenic variant. -
Autosomal recessive spinocerebellar ataxia 10 Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at