chrX-154030398-C-G
Variant summary
Our verdict is Uncertain significance. Variant got -3 ACMG points: 1P and 4B. BS2PM2_Supporting
This summary comes from the ClinGen Evidence Repository: The p.Ser477Thr (NM_004992.3) variant is observed in at least 2 unaffected individuals (PMID 12655490)(BS2). The p.Ser477Thr variant is observed in the MECP2 gene where a second pathogenic variant in the same gene is present in the patient (PMID 12655490); however, it is unknown if the variants are in cis or trans (BP5 - not met). The p.Ser477Thr variant in MECP2 is absent from gnomAD (PM2_supporting). In summary, the p.Ser477Thr variant in MECP2 is classified as a variant of uncertain significance based on the ACMG/AMP criteria (BS2, PM2_supporting). LINK:https://erepo.genome.network/evrepo/ui/classification/CA170245/MONDO:0010726/016
Frequency
Consequence
NM_001110792.2 missense
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.1466G>C | p.Ser489Thr | missense_variant | 3/3 | ENST00000453960.7 | |
MECP2 | NM_004992.4 | c.1430G>C | p.Ser477Thr | missense_variant | 4/4 | ENST00000303391.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MECP2 | ENST00000453960.7 | c.1466G>C | p.Ser489Thr | missense_variant | 3/3 | 1 | NM_001110792.2 | ||
MECP2 | ENST00000303391.11 | c.1430G>C | p.Ser477Thr | missense_variant | 4/4 | 1 | NM_004992.4 | P1 | |
MECP2 | ENST00000628176.2 | c.*802G>C | 3_prime_UTR_variant | 5/5 | 3 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD4 exome AF: 0.00000728 AC: 8AN: 1098234Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 3AN XY: 363588
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
Rett syndrome Uncertain:2
Uncertain significance, reviewed by expert panel | curation | ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel | Dec 13, 2021 | The p.Ser477Thr (NM_004992.3) variant is observed in at least 2 unaffected individuals (PMID 12655490)(BS2). The p.Ser477Thr variant is observed in the MECP2 gene where a second pathogenic variant in the same gene is present in the patient (PMID 12655490); however, it is unknown if the variants are in cis or trans (BP5 - not met). The p.Ser477Thr variant in MECP2 is absent from gnomAD (PM2_supporting). In summary, the p.Ser477Thr variant in MECP2 is classified as a variant of uncertain significance based on the ACMG/AMP criteria (BS2, PM2_supporting). - |
Uncertain significance, 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 a variant of uncertain significance. At least the following criteria are met: The variant is observed in at least 2 individuals with no features of Rett Syndrome (BS2).PMID: 12655490 This variant is absent from gnomAD (PM2_Supporting). - |
not specified Benign:1
Benign, no assertion criteria provided | curation | RettBASE | Nov 01, 2007 | - - |
Severe neonatal-onset encephalopathy with microcephaly Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at