rs267608457
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001110792.2(MECP2):c.411del(p.Asn138IlefsTer13) variant causes a frameshift, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. I137I) has been classified as Benign.
Frequency
Consequence
NM_001110792.2 frameshift, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MECP2 | NM_001110792.2 | c.411del | p.Asn138IlefsTer13 | frameshift_variant, splice_region_variant | 2/3 | ENST00000453960.7 | |
MECP2 | NM_004992.4 | c.375del | p.Asn126IlefsTer13 | frameshift_variant, splice_region_variant | 3/4 | ENST00000303391.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MECP2 | ENST00000453960.7 | c.411del | p.Asn138IlefsTer13 | frameshift_variant, splice_region_variant | 2/3 | 1 | NM_001110792.2 | ||
MECP2 | ENST00000303391.11 | c.375del | p.Asn126IlefsTer13 | frameshift_variant, splice_region_variant | 3/4 | 1 | NM_004992.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 24
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 24
ClinVar
Submissions by phenotype
Rett syndrome Pathogenic:2
Pathogenic, no assertion criteria provided | curation | RettBASE | Feb 18, 2008 | - - |
Pathogenic, criteria provided, single submitter | curation | Centre for Population Genomics, CPG | Mar 14, 2024 | This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria. Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders Specifications to the ACMG/AMP Variant Interpretation Guidelines VCEP 3.0, this variant is classified as pathogenic. At least the following criteria are met: Predicted to result in loss of function, and LOF is a known mechanism of disease (PVS1). This variant is absent from gnomAD (PM2_Supporting). Has been observed in at least 2 individuals with phenotypes consistent with MECP2-related disease (PS4_Supporting). PubMed: 10991688‚Äö 15737703 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at