rs1557135441
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_001110792.2(MECP2):c.1159_1227del(p.Ser387_Glu409del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000000915 in 1,093,222 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 17)
Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )
Consequence
MECP2
NM_001110792.2 inframe_deletion
NM_001110792.2 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.66
Genes affected
MECP2 (HGNC:6990): (methyl-CpG binding protein 2) DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of nuclear proteins related by the presence in each of a methyl-CpG binding domain (MBD). Each of these proteins, with the exception of MBD3, is capable of binding specifically to methylated DNA. MECP2, MBD1 and MBD2 can also repress transcription from methylated gene promoters. In contrast to other MBD family members, MECP2 is X-linked and subject to X inactivation. MECP2 is dispensible in stem cells, but is essential for embryonic development. MECP2 gene mutations are the cause of most cases of Rett syndrome, a progressive neurologic developmental disorder and one of the most common causes of cognitive disability in females. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_001110792.2.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MECP2 | NM_001110792.2 | c.1159_1227del | p.Ser387_Glu409del | inframe_deletion | 3/3 | ENST00000453960.7 | NP_001104262.1 | |
MECP2 | NM_004992.4 | c.1123_1191del | p.Ser375_Glu397del | inframe_deletion | 4/4 | ENST00000303391.11 | NP_004983.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MECP2 | ENST00000303391.11 | c.1123_1191del | p.Ser375_Glu397del | inframe_deletion | 4/4 | 1 | NM_004992.4 | ENSP00000301948 | P1 | |
MECP2 | ENST00000453960.7 | c.1159_1227del | p.Ser387_Glu409del | inframe_deletion | 3/3 | 1 | NM_001110792.2 | ENSP00000395535 | ||
MECP2 | ENST00000407218.5 | c.*495_*563del | 3_prime_UTR_variant | 4/4 | 5 | ENSP00000384865 | ||||
MECP2 | ENST00000628176.2 | c.*495_*563del | 3_prime_UTR_variant | 5/5 | 3 | ENSP00000486978 |
Frequencies
GnomAD3 genomes Cov.: 17
GnomAD3 genomes
Cov.:
17
GnomAD4 exome AF: 9.15e-7 AC: 1AN: 1093222Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 360664
GnomAD4 exome
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GnomAD4 genome Cov.: 17
GnomAD4 genome
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17
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Rett syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | curation | Centre for Population Genomics, CPG | Jan 12, 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 1 individual with no features of Rett Syndrome (BS2_Supporting) - |
Uncertain significance, no assertion criteria provided | curation | RettBASE | Apr 10, 2002 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at