rs587777421
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2_SupportingPVS1_Moderate
This summary comes from the ClinGen Evidence Repository: The p.Glu483Ter variant in MECP2 (NM_004992.4) is predicted to cause a premature stop codon that leads to a truncated or absent protein in a gene where loss-of-function is an established mechanism. While loss-of-function variants are commonly observed in affected individuals in this gene, there is a paucity of these variants in this region of the gene to date (PVS1_Moderate). The p.Glu483Ter variant in MECP2 is absent from gnomAD (PM2_Supporting). This variant was reported in two male siblings with autism who inherited the p.Glu483Ter variant from their unaffected mother (PMID 23352163). In summary, the p.Glu483Ter variant in MECP2 is classified as variant of unknown significance based on the ACMG/AMP criteria (PVS1_Moderate, PM2_Supporting). LINK:https://erepo.genome.network/evrepo/ui/classification/CA156430/MONDO:0010726/036
Frequency
Consequence
NM_001110792.2 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MECP2 | NM_001110792.2 | c.1483G>T | p.Glu495Ter | stop_gained | 3/3 | ENST00000453960.7 | |
MECP2 | NM_004992.4 | c.1447G>T | p.Glu483Ter | stop_gained | 4/4 | ENST00000303391.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MECP2 | ENST00000453960.7 | c.1483G>T | p.Glu495Ter | stop_gained | 3/3 | 1 | NM_001110792.2 | ||
MECP2 | ENST00000303391.11 | c.1447G>T | p.Glu483Ter | stop_gained | 4/4 | 1 | NM_004992.4 | P1 | |
MECP2 | ENST00000628176.2 | c.*819G>T | 3_prime_UTR_variant | 5/5 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 22
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | May 27, 2021 | 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; This variant is associated with the following publications: (PMID: 28263302, 23352163, 24878448, 23352160) - |
Rett syndrome Uncertain:1
Uncertain significance, reviewed by expert panel | curation | ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel | Aug 23, 2023 | The p.Glu483Ter variant in MECP2 (NM_004992.4) is predicted to cause a premature stop codon that leads to a truncated or absent protein in a gene where loss-of-function is an established mechanism. While loss-of-function variants are commonly observed in affected individuals in this gene, there is a paucity of these variants in this region of the gene to date (PVS1_Moderate). The p.Glu483Ter variant in MECP2 is absent from gnomAD (PM2_Supporting). This variant was reported in two male siblings with autism who inherited the p.Glu483Ter variant from their unaffected mother (PMID 23352163). In summary, the p.Glu483Ter variant in MECP2 is classified as variant of unknown significance based on the ACMG/AMP criteria (PVS1_Moderate, PM2_Supporting). - |
Autism, susceptibility to, X-linked 3 Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Jan 23, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at