rs267608504
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_Very_StrongBP7BS2_Supporting
The NM_001110792.2(MECP2):c.639G>A(p.Ala213=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000909 in 1,209,555 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 43 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001110792.2 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MECP2 | NM_001110792.2 | c.639G>A | p.Ala213= | synonymous_variant | 3/3 | ENST00000453960.7 | NP_001104262.1 | |
MECP2 | NM_004992.4 | c.603G>A | p.Ala201= | synonymous_variant | 4/4 | ENST00000303391.11 | NP_004983.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MECP2 | ENST00000453960.7 | c.639G>A | p.Ala213= | synonymous_variant | 3/3 | 1 | NM_001110792.2 | ENSP00000395535 | ||
MECP2 | ENST00000303391.11 | c.603G>A | p.Ala201= | synonymous_variant | 4/4 | 1 | NM_004992.4 | ENSP00000301948 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000988 AC: 11AN: 111288Hom.: 0 Cov.: 23 AF XY: 0.0000597 AC XY: 2AN XY: 33478
GnomAD3 exomes AF: 0.0000763 AC: 14AN: 183468Hom.: 0 AF XY: 0.000133 AC XY: 9AN XY: 67902
GnomAD4 exome AF: 0.0000901 AC: 99AN: 1098267Hom.: 0 Cov.: 35 AF XY: 0.000113 AC XY: 41AN XY: 363621
GnomAD4 genome AF: 0.0000988 AC: 11AN: 111288Hom.: 0 Cov.: 23 AF XY: 0.0000597 AC XY: 2AN XY: 33478
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 25, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | curation | RettBASE | Dec 03, 2010 | - - |
Severe neonatal-onset encephalopathy with microcephaly Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 21, 2023 | - - |
Rett syndrome Benign:1
Benign, criteria provided, single submitter | curation | Centre for Population Genomics, CPG | Mar 22, 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 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 3.0 (BA1). - |
MECP2-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 06, 2021 | This variant is classified as likely 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