rs267608589
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM4
The NM_001110792.2(MECP2):c.1198_1233del(p.Pro400_Pro411del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P400P) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 18)
Consequence
MECP2
NM_001110792.2 inframe_deletion
NM_001110792.2 inframe_deletion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 3.50
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.
PM1
?
In a hotspot region, there are 5 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 13 benign, 11 uncertain in NM_001110792.2
PM4
?
Nonframeshift variant in NON repetitive region in NM_001110792.2.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MECP2 | NM_001110792.2 | c.1198_1233del | p.Pro400_Pro411del | inframe_deletion | 3/3 | ENST00000453960.7 | |
MECP2 | NM_004992.4 | c.1162_1197del | p.Pro388_Pro399del | inframe_deletion | 4/4 | ENST00000303391.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MECP2 | ENST00000303391.11 | c.1162_1197del | p.Pro388_Pro399del | inframe_deletion | 4/4 | 1 | NM_004992.4 | P1 | |
MECP2 | ENST00000453960.7 | c.1198_1233del | p.Pro400_Pro411del | inframe_deletion | 3/3 | 1 | NM_001110792.2 | ||
MECP2 | ENST00000407218.5 | c.*534_*569del | 3_prime_UTR_variant | 4/4 | 5 | ||||
MECP2 | ENST00000628176.2 | c.*534_*569del | 3_prime_UTR_variant | 5/5 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 18
GnomAD3 genomes
?
Cov.:
18
GnomAD3 exomes AF: 0.00000571 AC: 1AN: 175276Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 63870
GnomAD3 exomes
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AC:
1
AN:
175276
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0
AN XY:
63870
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 18
GnomAD4 genome
?
Cov.:
18
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at