chr11-26441958-G-C
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_031418.4(ANO3):c.87G>C(p.Ser29=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000601 in 1,613,716 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000052 ( 1 hom. )
Consequence
ANO3
NM_031418.4 synonymous
NM_031418.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.473
Genes affected
ANO3 (HGNC:14004): (anoctamin 3) The protein encoded by this gene belongs to the TMEM16 family of predicted membrane proteins, that are also known as anoctamins. While little is known about the function of this gene, mutations in this gene have been associated with some cases of autosomal dominant craniocervical dystonia. Cells from individuals with a mutation in this gene exhibited abnormalities in endoplasmic reticulum-dependent calcium signaling. Studies in rat show that the rat ortholog of this protein interacts with, and modulates the activity of a sodium-activated potassium channel. Deletion of this gene caused increased pain sensitivity in the rat model system. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 11-26441958-G-C is Benign according to our data. Variant chr11-26441958-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 696389.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.473 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000138 (21/152096) while in subpopulation EAS AF= 0.00155 (8/5160). AF 95% confidence interval is 0.000771. There are 0 homozygotes in gnomad4. There are 7 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 21 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANO3 | NM_031418.4 | c.87G>C | p.Ser29= | synonymous_variant | 2/27 | ENST00000256737.8 | |
ANO3 | NM_001313726.2 | c.270G>C | p.Ser90= | synonymous_variant | 3/28 | ||
ANO3 | XM_047427399.1 | c.87G>C | p.Ser29= | synonymous_variant | 2/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANO3 | ENST00000256737.8 | c.87G>C | p.Ser29= | synonymous_variant | 2/27 | 1 | NM_031418.4 | P3 | |
ANO3 | ENST00000672621.1 | c.270G>C | p.Ser90= | synonymous_variant | 3/28 | ||||
ANO3 | ENST00000525139.5 | c.39G>C | p.Ser13= | synonymous_variant | 2/27 | 5 | |||
ANO3 | ENST00000531646.1 | c.87G>C | p.Ser29= | synonymous_variant | 2/5 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 151980Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000957 AC: 24AN: 250912Hom.: 0 AF XY: 0.0000738 AC XY: 10AN XY: 135586
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GnomAD4 exome AF: 0.0000520 AC: 76AN: 1461620Hom.: 1 Cov.: 30 AF XY: 0.0000413 AC XY: 30AN XY: 727104
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
ANO3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 22, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Dystonic disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 26, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at