chrX-129540464-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000276.4(OCRL):c.25G>A(p.Ala9Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict 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. A9A) has been classified as Likely benign.
Frequency
Consequence
NM_000276.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OCRL | NM_000276.4 | c.25G>A | p.Ala9Thr | missense_variant | 1/24 | ENST00000371113.9 | |
OCRL | NM_001318784.2 | c.25G>A | p.Ala9Thr | missense_variant | 1/24 | ||
OCRL | NM_001587.4 | c.25G>A | p.Ala9Thr | missense_variant | 1/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OCRL | ENST00000371113.9 | c.25G>A | p.Ala9Thr | missense_variant | 1/24 | 1 | NM_000276.4 | P1 | |
OCRL | ENST00000357121.5 | c.25G>A | p.Ala9Thr | missense_variant | 1/23 | 1 | |||
OCRL | ENST00000691455.1 | c.25G>A | p.Ala9Thr | missense_variant, NMD_transcript_variant | 1/18 | ||||
OCRL | ENST00000486673.1 | n.91+525G>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 21
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 21
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 17, 2017 | The A9T variant in the OCRL gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The A9T variant is not observed in large population cohorts; however, limited data are available (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A9T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret A9T as a variant of uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at