chr11-22255400-C-T
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_213599.3(ANO5):โc.1210C>Tโ(p.Arg404Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000745 in 1,610,810 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 Pathogenic (โ โ ). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_213599.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANO5 | NM_213599.3 | c.1210C>T | p.Arg404Ter | stop_gained | 13/22 | ENST00000324559.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANO5 | ENST00000324559.9 | c.1210C>T | p.Arg404Ter | stop_gained | 13/22 | 1 | NM_213599.3 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 151856Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248960Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134734
GnomAD4 exome AF: 0.00000480 AC: 7AN: 1458954Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 725880
GnomAD4 genome AF: 0.0000329 AC: 5AN: 151856Hom.: 0 Cov.: 32 AF XY: 0.0000405 AC XY: 3AN XY: 74146
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jul 20, 2023 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Reported previously along with a second variant, in individuals reported to have limb-girdle muscular dystrophy type 2L and Miyoshi-like muscular dystrophy (Sarkozy et al., 2012; Wahbi et al., 2013); This variant is associated with the following publications: (PMID: 23041008, 32819793, 32367299, 32528171, 22980763) - |
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 23, 2015 | - - |
ANO5-related disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 06, 2023 | The ANO5 c.1210C>T variant is predicted to result in premature protein termination (p.Arg404*). This variant was reported in an individuals with autosomal recessive ANO5-related muscle disorders (Sarkozy et al 2012. PubMed ID: 22980763; Wahbi K et al 2012. PubMed ID: 23041008; Supp. Table 4 in Tรถpf A et al 2020. PubMed ID: 32528171). This variant is reported in 0.0050% of alleles in individuals of East Asian descent in gnomAD. Nonsense variants in ANO5 are expected to be pathogenic. This variant is interpreted as pathogenic. - |
Gnathodiaphyseal dysplasia;C1969785:Autosomal recessive limb-girdle muscular dystrophy type 2L Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 05, 2021 | This sequence change creates a premature translational stop signal (p.Arg404*) in the ANO5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ANO5 are known to be pathogenic (PMID: 21186264, 23606453, 25891276, 30919934). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with autosomal recessive ANO5-related conditions (PMID: 22980763, 32367299, 32819793). ClinVar contains an entry for this variant (Variation ID: 217143). For these reasons, this variant has been classified as Pathogenic. - |
Autosomal recessive limb-girdle muscular dystrophy type 2L Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 14, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at