rs786205037
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PM5PP3
The NM_001110792.2(MECP2):c.413A>G(p.Asn138Ser) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N138D) has been classified as Uncertain significance.
Frequency
Consequence
NM_001110792.2 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MECP2 | NM_001110792.2 | c.413A>G | p.Asn138Ser | missense_variant, splice_region_variant | 2/3 | ENST00000453960.7 | |
MECP2 | NM_004992.4 | c.377A>G | p.Asn126Ser | missense_variant, splice_region_variant | 3/4 | ENST00000303391.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MECP2 | ENST00000453960.7 | c.413A>G | p.Asn138Ser | missense_variant, splice_region_variant | 2/3 | 1 | NM_001110792.2 | ||
MECP2 | ENST00000303391.11 | c.377A>G | p.Asn126Ser | missense_variant, splice_region_variant | 3/4 | 1 | NM_004992.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD4 exome Cov.: 29
GnomAD4 genome ? Cov.: 24
ClinVar
Submissions by phenotype
Severe neonatal-onset encephalopathy with microcephaly Uncertain:1
Uncertain significance, no assertion criteria provided | curation | RettBASE | Jul 13, 2010 | - - |
Rett syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | curation | Centre for Population Genomics, CPG | Mar 15, 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 a variant of uncertain significance. At least the following criteria are met: Occurs in the well-characterized Methyl-DNA binding (MDB) functional domain of MECP2 (PM1). This variant is absent from gnomAD (PM2_Supporting). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at