chr3-43576721-C-T
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_018075.5(ANO10):c.1133G>A(p.Arg378Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000488 in 1,614,094 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0026 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00027 ( 2 hom. )
Consequence
ANO10
NM_018075.5 missense
NM_018075.5 missense
Scores
3
6
10
Clinical Significance
Conservation
PhyloP100: 5.01
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 -13 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.010655791).
BP6
Variant 3-43576721-C-T is Benign according to our data. Variant chr3-43576721-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 345187.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=3}.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00259 (394/152210) while in subpopulation AFR AF= 0.00915 (380/41522). AF 95% confidence interval is 0.00839. There are 2 homozygotes in gnomad4. There are 182 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANO10 | NM_018075.5 | c.1133G>A | p.Arg378Gln | missense_variant | 6/13 | ENST00000292246.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANO10 | ENST00000292246.8 | c.1133G>A | p.Arg378Gln | missense_variant | 6/13 | 1 | NM_018075.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00259 AC: 394AN: 152092Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000705 AC: 177AN: 251168Hom.: 1 AF XY: 0.000560 AC XY: 76AN XY: 135740
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GnomAD4 exome AF: 0.000269 AC: 393AN: 1461884Hom.: 2 Cov.: 32 AF XY: 0.000245 AC XY: 178AN XY: 727240
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GnomAD4 genome AF: 0.00259 AC: 394AN: 152210Hom.: 2 Cov.: 32 AF XY: 0.00245 AC XY: 182AN XY: 74406
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Autosomal recessive spinocerebellar ataxia 10 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
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. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 19, 2021 | - - |
ANO10-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 30, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Uncertain
D;T;D;T
Sift4G
Benign
T;T;D;D
Polyphen
D;D;.;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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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