rs61750245
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001110792.2(MECP2):c.855G>T(p.Gly285=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000542 in 1,210,680 control chromosomes in the GnomAD database, including 1 homozygotes. There are 227 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G285G) has been classified as Likely benign.
Frequency
Consequence
NM_001110792.2 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MECP2 | NM_001110792.2 | c.855G>T | p.Gly285= | synonymous_variant | 3/3 | ENST00000453960.7 | |
MECP2 | NM_004992.4 | c.819G>T | p.Gly273= | synonymous_variant | 4/4 | ENST00000303391.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MECP2 | ENST00000453960.7 | c.855G>T | p.Gly285= | synonymous_variant | 3/3 | 1 | NM_001110792.2 | ||
MECP2 | ENST00000303391.11 | c.819G>T | p.Gly273= | synonymous_variant | 4/4 | 1 | NM_004992.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000569 AC: 64AN: 112438Hom.: 0 Cov.: 23 AF XY: 0.000491 AC XY: 17AN XY: 34596
GnomAD3 exomes AF: 0.000461 AC: 84AN: 182177Hom.: 0 AF XY: 0.000490 AC XY: 33AN XY: 67413
GnomAD4 exome AF: 0.000539 AC: 592AN: 1098189Hom.: 1 Cov.: 35 AF XY: 0.000578 AC XY: 210AN XY: 363563
GnomAD4 genome ? AF: 0.000569 AC: 64AN: 112491Hom.: 0 Cov.: 23 AF XY: 0.000490 AC XY: 17AN XY: 34659
ClinVar
Submissions by phenotype
Rett syndrome Benign:3
Benign, criteria provided, single submitter | curation | Centre for Population Genomics, CPG | Aug 14, 2023 | 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 2.0, this variant is classified as Benign. At least the following criteria are met: The allele frequency of this variant in at least one population in gnomAD is higher than the 0.03% threshold defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders VCEP 2.0 (BA1). - |
Benign, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, Children's Mercy Hospital and Clinics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 01, 2015 | The variant of interest causes a synonymous change with 3/5 in silico programs predicting no significant effect on splicing, although these predictions have yet to be functionally assessed. The variant of interest was observed in a large, broad control population, ExAC, with an allele frequency of 48/85990 (1/1791 including 18 hemizygotes), which exceeds the maximum expected allele frequency for a pathogenic MECP2 variant. The variant of interest has been reported in affected individuals via publications and reputable clinical laboratories/databases with a classification of "benign/polymorphism." Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Benign. - |
not specified Benign:2
Benign, no assertion criteria provided | curation | RettBASE | Dec 05, 2013 | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 26, 2018 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Severe neonatal-onset encephalopathy with microcephaly Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 27, 2017 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
MECP2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 22, 2021 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at