rs587783104
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_001110792.2(MECP2):c.1042C>G(p.Leu348Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000911 in 1,098,252 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★★). Synonymous variant affecting the same amino acid position (i.e. L348L) has been classified as Likely benign.
Frequency
Consequence
NM_001110792.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MECP2 | NM_001110792.2 | c.1042C>G | p.Leu348Val | missense_variant | 3/3 | ENST00000453960.7 | |
MECP2 | NM_004992.4 | c.1006C>G | p.Leu336Val | missense_variant | 4/4 | ENST00000303391.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MECP2 | ENST00000453960.7 | c.1042C>G | p.Leu348Val | missense_variant | 3/3 | 1 | NM_001110792.2 | ||
MECP2 | ENST00000303391.11 | c.1006C>G | p.Leu336Val | missense_variant | 4/4 | 1 | NM_004992.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD4 exome AF: 0.00000911 AC: 10AN: 1098252Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 1AN XY: 363606
GnomAD4 genome ? Cov.: 23
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:2
Likely pathogenic, criteria provided, single submitter | research | Department Of Translational Genomics (developmental Genetics Section), King Faisal Specialist Hospital & Research Centre | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 30, 2016 | The L336V variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The L336V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across mammals but not in distantly related species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Feb 25, 2021 | - - |
Rett syndrome Uncertain:1
Uncertain significance, reviewed by expert panel | curation | ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel | Dec 13, 2021 | The p.Leu336Val variant (NM_004992.3) in MECP2 is absent from gnomAD (PM2_supporting). The p.Leu336Val variant is not currently published and is not present in additional databases (internal and publicly available), therefore, no additional criteria are applicable at this time. In summary, the p.Leu336Val variant in MECP2 is classified as a variant of uncertain significance based on the ACMG/AMP criteria (PM2_supporting). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at