1-29196234-A-C
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_016011.5(MECR):āc.855T>Gā(p.Tyr285*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,360 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 Pathogenic (ā ā ). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_016011.5 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MECR | NM_016011.5 | c.855T>G | p.Tyr285* | stop_gained | 8/10 | ENST00000263702.11 | NP_057095.4 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461360Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726906
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | MECR: PVS1, PM2 - |
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 14, 2023 | For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Tyr285*) in the MECR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MECR are known to be pathogenic (PMID: 27817865). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with dystonia (PMID: 27817865). ClinVar contains an entry for this variant (Variation ID: 374879). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jan 13, 2022 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Identified in a patient with clinical features consistent with MECR-related disorder in published literature (Heimer et al., 2016); This variant is associated with the following publications: (PMID: 27817865) - |
Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 08, 2024 | - - |
Optic atrophy;C0752202:Childhood Onset Dystonias Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | Dec 01, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at