rs778855963
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001008212.2(OPTN):c.628G>A(p.Ala210Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,613,686 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_001008212.2 missense, splice_region
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OPTN | NM_001008212.2 | c.628G>A | p.Ala210Thr | missense_variant, splice_region_variant | 7/15 | ENST00000378747.8 | |
OPTN | NM_001008211.1 | c.628G>A | p.Ala210Thr | missense_variant, splice_region_variant | 8/16 | ||
OPTN | NM_001008213.1 | c.628G>A | p.Ala210Thr | missense_variant, splice_region_variant | 8/16 | ||
OPTN | NM_021980.4 | c.628G>A | p.Ala210Thr | missense_variant, splice_region_variant | 6/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OPTN | ENST00000378747.8 | c.628G>A | p.Ala210Thr | missense_variant, splice_region_variant | 7/15 | 1 | NM_001008212.2 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152120Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.0000376 AC: 55AN: 1461566Hom.: 0 Cov.: 31 AF XY: 0.0000371 AC XY: 27AN XY: 727120
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152120Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74306
ClinVar
Submissions by phenotype
OPTN-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 01, 2022 | The OPTN c.628G>A variant is predicted to result in the amino acid substitution p.Ala210Thr. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 23, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at