rs267608347
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate
The NM_001110792.2(MECP2):c.*36G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000911 in 1,097,864 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 0.0000091 ( 0 hom. 4 hem. )
Failed GnomAD Quality Control
Consequence
MECP2
NM_001110792.2 3_prime_UTR
NM_001110792.2 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.95
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 Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
Variant X-154030331-C-G is Benign according to our data. Variant chrX-154030331-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 143266.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154030331-C-G is described in Lovd as [Benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MECP2 | NM_001110792.2 | c.*36G>C | 3_prime_UTR_variant | 3/3 | ENST00000453960.7 | ||
MECP2 | NM_004992.4 | c.*36G>C | 3_prime_UTR_variant | 4/4 | ENST00000303391.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MECP2 | ENST00000303391.11 | c.*36G>C | 3_prime_UTR_variant | 4/4 | 1 | NM_004992.4 | P1 | ||
MECP2 | ENST00000453960.7 | c.*36G>C | 3_prime_UTR_variant | 3/3 | 1 | NM_001110792.2 | |||
MECP2 | ENST00000628176.2 | c.*869G>C | 3_prime_UTR_variant | 5/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 111229Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33433 FAILED QC
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GnomAD4 exome AF: 0.00000911 AC: 10AN: 1097864Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 4AN XY: 363244
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GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 111229Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33433
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, no assertion criteria provided | curation | RettBASE | May 31, 2006 | - - |
Rett syndrome Benign:1
Likely 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 to the ACMG/AMP Variant Interpretation Guidelines VCEP 2.0 , this variant is classified as likely benign. At least the following criteria are met: The allele frequency of this variant in TOPMED is between 0.008% and 0.03% (BS1).The variant is observed in at least 1 individual with no features of Rett Syndrome (BS2_Supporting). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at