rs776800006
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001042472.3(ABHD12):c.874C>T(p.Arg292Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000808 in 1,608,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001042472.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABHD12 | NM_001042472.3 | c.874C>T | p.Arg292Ter | stop_gained | 10/13 | ENST00000339157.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABHD12 | ENST00000339157.10 | c.874C>T | p.Arg292Ter | stop_gained | 10/13 | 2 | NM_001042472.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250390Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135420
GnomAD4 exome AF: 0.00000824 AC: 12AN: 1456368Hom.: 0 Cov.: 29 AF XY: 0.00000966 AC XY: 7AN XY: 724864
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74354
ClinVar
Submissions by phenotype
PHARC syndrome Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Molecular Genetics, Royal Melbourne Hospital | Apr 11, 2023 | This sequence change in ABHD12 is a nonsense variant predicted to cause a premature stop codon, p.(Arg292*), in biologically relevant exon 10/13 leading to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism. The highest population minor allele frequency in the population database gnomAD v2.1 is 0.003% (1/30,588 alleles) in the South Asian population, consistent with a recessive disease. This variant has been observed with an ABHD12 variant of uncertain significance in an individual with an adult-onset movement disorder (PMID: 34085946). Based on the classification scheme RMH Modified ACMG Guidelines v1.5.1, this variant is classified as LIKELY PATHOGENIC. Following criteria are met: PVS1, PM2_Supporting. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Equipe Genetique des Anomalies du Developpement, Université de Bourgogne | Mar 22, 2017 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Oct 16, 2017 | The R292X nonsense variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. R292X is not observed at a significant frequency in large population cohorts (Lek et al., 2016). In summary, we consider this variant to be pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at