rs61746297
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_031418.4(ANO3):c.164C>T(p.Ser55Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00731 in 1,614,172 control chromosomes in the GnomAD database, including 62 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 0.0045 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0076 ( 60 hom. )
Consequence
ANO3
NM_031418.4 missense
NM_031418.4 missense
Scores
8
10
Clinical Significance
Conservation
PhyloP100: 4.58
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.008046448).
BP6
?
Variant 11-26442035-C-T is Benign according to our data. Variant chr11-26442035-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 412872.We mark this variant Likely_benign, oryginal submissions are: {Benign=3, Likely_benign=1, Uncertain_significance=1}. Variant chr11-26442035-C-T is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0045 (686/152330) while in subpopulation NFE AF= 0.00745 (507/68032). AF 95% confidence interval is 0.00692. There are 2 homozygotes in gnomad4. There are 327 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 686 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANO3 | NM_031418.4 | c.164C>T | p.Ser55Phe | missense_variant | 2/27 | ENST00000256737.8 | |
ANO3 | NM_001313726.2 | c.347C>T | p.Ser116Phe | missense_variant | 3/28 | ||
ANO3 | XM_047427399.1 | c.164C>T | p.Ser55Phe | missense_variant | 2/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANO3 | ENST00000256737.8 | c.164C>T | p.Ser55Phe | missense_variant | 2/27 | 1 | NM_031418.4 | P3 | |
ANO3 | ENST00000672621.1 | c.347C>T | p.Ser116Phe | missense_variant | 3/28 | ||||
ANO3 | ENST00000525139.5 | c.116C>T | p.Ser39Phe | missense_variant | 2/27 | 5 | |||
ANO3 | ENST00000531646.1 | c.164C>T | p.Ser55Phe | missense_variant | 2/5 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.00451 AC: 686AN: 152212Hom.: 2 Cov.: 32
GnomAD3 genomes
?
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686
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GnomAD3 exomes AF: 0.00519 AC: 1306AN: 251454Hom.: 5 AF XY: 0.00532 AC XY: 723AN XY: 135896
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GnomAD4 exome AF: 0.00760 AC: 11110AN: 1461842Hom.: 60 Cov.: 31 AF XY: 0.00746 AC XY: 5426AN XY: 727220
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GnomAD4 genome ? AF: 0.00450 AC: 686AN: 152330Hom.: 2 Cov.: 32 AF XY: 0.00439 AC XY: 327AN XY: 74484
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ESP6500AA
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ExAC
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608
Asia WGS
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:6
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | ANO3: BP4, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 05, 2019 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 28, 2022 | The c.164C>T (p.S55F) alteration is located in exon 2 (coding exon 2) of the ANO3 gene. This alteration results from a C to T substitution at nucleotide position 164, causing the serine (S) at amino acid position 55 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Dystonia 24 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Dystonic disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
1.0
.;D;.
Vest4
MVP
MPC
0.77
ClinPred
T
GERP RS
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