rs780333963
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP3_StrongPP5_Moderate
The NM_130837.3(OPA1):c.1033C>T(p.Arg345Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,448,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R345Q) has been classified as Likely pathogenic.
Frequency
Consequence
NM_130837.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OPA1 | NM_130837.3 | c.1033C>T | p.Arg345Trp | missense_variant, splice_region_variant | 10/31 | ENST00000361510.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OPA1 | ENST00000361510.8 | c.1033C>T | p.Arg345Trp | missense_variant, splice_region_variant | 10/31 | 5 | NM_130837.3 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250406Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135304
GnomAD4 exome AF: 0.00000276 AC: 4AN: 1448260Hom.: 0 Cov.: 25 AF XY: 0.00000555 AC XY: 4AN XY: 721230
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Abnormal brain morphology Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at