chr3-193614715-T-C
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_130837.3(OPA1):c.33-8T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,605,474 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_130837.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OPA1 | NM_130837.3 | c.33-8T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000361510.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OPA1 | ENST00000361510.8 | c.33-8T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_130837.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152240Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000281 AC: 7AN: 248736Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134706
GnomAD4 exome AF: 0.0000248 AC: 36AN: 1453234Hom.: 0 Cov.: 31 AF XY: 0.0000180 AC XY: 13AN XY: 723642
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152240Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74390
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 05, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 20, 2023 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 14, 2024 | Variant summary: OPA1 c.33-8T>C alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2.8e-05 in 248736 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.33-8T>C in individuals affected with OPA1-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 195308). Based on the evidence outlined above, the variant was classified as uncertain significance. - |
OPA1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 24, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at