rs794726680
Variant names:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_018075.5(ANO10):c.1150_1151delTT(p.Leu384AsnfsTer91) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
ANO10
NM_018075.5 frameshift
NM_018075.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.29
Genes affected
ANO10 (HGNC:25519): (anoctamin 10) The transmembrane protein encoded by this gene belongs to the anoctamin family of calcium-activated chloride channels, also known as the transmembrane 16 family. The encoded protein contains eight transmembrane domains with cytosolic N- and C-termini. Defects in this gene may cause autosomal recessive spinocerebellar ataxia-10. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 3-43576702-TAA-T is Pathogenic according to our data. Variant chr3-43576702-TAA-T is described in ClinVar as [Pathogenic]. Clinvar id is 31058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ANO10 | NM_018075.5 | c.1150_1151delTT | p.Leu384AsnfsTer91 | frameshift_variant | Exon 6 of 13 | ENST00000292246.8 | NP_060545.3 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461870Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727234
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Autosomal recessive spinocerebellar ataxia 10 Pathogenic:2
Dec 10, 2010
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only
- -
Jan 10, 2024
Fulgent Genetics, Fulgent Genetics
Significance: Pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
not provided Pathogenic:1
Oct 23, 2020
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Significance: Pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at