rs747575706
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting
The NM_213599.3(ANO5):c.88C>G(p.Gln30Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000993 in 1,611,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict 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 Uncertain significance (★).
Frequency
Consequence
NM_213599.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANO5 | NM_213599.3 | c.88C>G | p.Gln30Glu | missense_variant, splice_region_variant | 3/22 | ENST00000324559.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANO5 | ENST00000324559.9 | c.88C>G | p.Gln30Glu | missense_variant, splice_region_variant | 3/22 | 1 | NM_213599.3 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151918Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 250640Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135458
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1459950Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 726354
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151918Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74202
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 | Aug 16, 2023 | This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 30 of the ANO5 protein (p.Gln30Glu). This variant is present in population databases (rs747575706, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with ANO5-related conditions. 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 468847). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at