chr3-43366538-G-A
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_018075.5(ANO10):c.*368C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00196 in 386,632 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0042 ( 6 hom., cov: 32)
Exomes 𝑓: 0.00053 ( 0 hom. )
Consequence
ANO10
NM_018075.5 3_prime_UTR
NM_018075.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.495
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 Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00416 (633/152304) while in subpopulation AFR AF= 0.0147 (610/41564). AF 95% confidence interval is 0.0137. There are 6 homozygotes in gnomad4. There are 302 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANO10 | NM_018075.5 | c.*368C>T | 3_prime_UTR_variant | 13/13 | ENST00000292246.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANO10 | ENST00000292246.8 | c.*368C>T | 3_prime_UTR_variant | 13/13 | 1 | NM_018075.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00415 AC: 632AN: 152186Hom.: 6 Cov.: 32
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GnomAD4 exome AF: 0.000533 AC: 125AN: 234328Hom.: 0 Cov.: 0 AF XY: 0.000466 AC XY: 59AN XY: 126544
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GnomAD4 genome AF: 0.00416 AC: 633AN: 152304Hom.: 6 Cov.: 32 AF XY: 0.00406 AC XY: 302AN XY: 74470
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive spinocerebellar ataxia 10 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at