11-22218276-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PP3_StrongPP5BS2_Supporting
The NM_213599.3(ANO5):c.169C>T(p.Arg57Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_213599.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151934Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251114Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135714
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461264Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 726930
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151934Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 74202
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:2
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Mar 07, 2025 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27671536, 23530687, 25864073, 30919934, 33963534, 35239206, 38127101, 36913258) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 12, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 18, 2020 | - - |
Miyoshi muscular dystrophy 3 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München | Feb 10, 2020 | - - |
Gnathodiaphyseal dysplasia;C1969785:Autosomal recessive limb-girdle muscular dystrophy type 2L Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 09, 2022 | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ANO5 protein function. ClinVar contains an entry for this variant (Variation ID: 432004). This missense change has been observed in individuals with autosomal recessive ANO5-related conditions (PMID: 23530687, 25864073, 33963534). This variant is present in population databases (no rsID available, gnomAD 0.009%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 57 of the ANO5 protein (p.Arg57Trp). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at