10-13112572-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001008212.2(OPTN):c.489A>T(p.Glu163Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. E163E) has been classified as Likely benign.
Frequency
Consequence
NM_001008212.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OPTN | NM_001008212.2 | c.489A>T | p.Glu163Asp | missense_variant | 5/15 | ENST00000378747.8 | NP_001008213.1 | |
OPTN | NM_001008211.1 | c.489A>T | p.Glu163Asp | missense_variant | 6/16 | NP_001008212.1 | ||
OPTN | NM_001008213.1 | c.489A>T | p.Glu163Asp | missense_variant | 6/16 | NP_001008214.1 | ||
OPTN | NM_021980.4 | c.489A>T | p.Glu163Asp | missense_variant | 4/14 | NP_068815.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OPTN | ENST00000378747.8 | c.489A>T | p.Glu163Asp | missense_variant | 5/15 | 1 | NM_001008212.2 | ENSP00000368021.3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152114Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727246
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152114Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74322
ClinVar
Submissions by phenotype
Primary open angle glaucoma;C1842026:Glaucoma 1, open angle, E;C3150692:Amyotrophic lateral sclerosis type 12 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 13, 2021 | 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 missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with OPTN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 163 of the OPTN protein (p.Glu163Asp). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at