chr19-45529085-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The ENST00000323060.4(OPA3):c.514C>T(p.Pro172Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000294 in 1,600,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
ENST00000323060.4 missense
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 |
---|---|---|---|---|---|---|---|
OPA3 | NM_001017989.3 | c.514C>T | p.Pro172Ser | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OPA3 | ENST00000323060.4 | c.514C>T | p.Pro172Ser | missense_variant | 2/2 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152102Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000806 AC: 19AN: 235622Hom.: 0 AF XY: 0.000108 AC XY: 14AN XY: 129622
GnomAD4 exome AF: 0.000315 AC: 456AN: 1448464Hom.: 0 Cov.: 30 AF XY: 0.000312 AC XY: 224AN XY: 718524
GnomAD4 genome ? AF: 0.0000920 AC: 14AN: 152102Hom.: 0 Cov.: 31 AF XY: 0.0000673 AC XY: 5AN XY: 74280
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 12, 2020 | The c.514C>T (p.P172S) alteration is located in exon 2 (coding exon 2) of the OPA3 gene. This alteration results from a C to T substitution at nucleotide position 514, causing the proline (P) at amino acid position 172 to be replaced by a serine (S). Based on data from the Genome Aggregation Database (gnomAD) database, the OPA3 c.514C>T alteration was observed in 0.0075% (20/266,956) of total alleles studied, with a frequency of 0.014% (17/119,898) in the European (non-Finnish) subpopulation. This amino acid position is not conserved on limited sequence alignment. The p.P172S alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 10, 2021 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at