chr11-22221210-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP7BS2_Supporting
The NM_213599.3(ANO5):c.294G>A(p.Ala98=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000677 in 1,592,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_213599.3 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANO5 | NM_213599.3 | c.294G>A | p.Ala98= | splice_region_variant, synonymous_variant | 5/22 | ENST00000324559.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANO5 | ENST00000324559.9 | c.294G>A | p.Ala98= | splice_region_variant, synonymous_variant | 5/22 | 1 | NM_213599.3 | P2 |
Frequencies
GnomAD3 genomes AF: 0.000612 AC: 93AN: 151910Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000690 AC: 172AN: 249194Hom.: 0 AF XY: 0.000779 AC XY: 105AN XY: 134744
GnomAD4 exome AF: 0.000684 AC: 986AN: 1440814Hom.: 0 Cov.: 28 AF XY: 0.000709 AC XY: 509AN XY: 717852
GnomAD4 genome AF: 0.000612 AC: 93AN: 151910Hom.: 0 Cov.: 32 AF XY: 0.000661 AC XY: 49AN XY: 74176
ClinVar
Submissions by phenotype
not provided Uncertain:5
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 28, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 26, 2020 | Functional studies indicate variant results in the in-frame loss of exons 4 and 5; however, control cells in this study also lacked exon 4 (Savarese et al., 2015); In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 25891276, 33023636) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 18, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | ANO5: PM2, PS3:Supporting, BP4, BP7 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 27, 2022 | Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is higher than would generally be expected for pathogenic variants in this gene (http://gnomad.broadinstitute.org). Computational tools yielded inconclusive predictions regarding the effect of this variant on RNA splicing. - |
ANO5-Related Muscle Diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Gnathodiaphyseal dysplasia;C1969785:Autosomal recessive limb-girdle muscular dystrophy type 2L Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at