rs774709754
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_213599.3(ANO5):āc.39A>Gā(p.Glu13=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_213599.3 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANO5 | NM_213599.3 | c.39A>G | p.Glu13= | splice_region_variant, synonymous_variant | 1/22 | ENST00000324559.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANO5 | ENST00000324559.9 | c.39A>G | p.Glu13= | splice_region_variant, synonymous_variant | 1/22 | 1 | NM_213599.3 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000410 AC: 1AN: 243962Hom.: 0 AF XY: 0.00000756 AC XY: 1AN XY: 132352
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460530Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 726456
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Gnathodiaphyseal dysplasia;C1969785:Autosomal recessive limb-girdle muscular dystrophy type 2L Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 06, 2018 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with ANO5-related disease. This variant is present in population databases (rs774709754, ExAC 0.01%). This sequence change affects codon 13 of the ANO5 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the ANO5 protein. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at