rs111565519
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The NM_001110792.2(MECP2):c.*489G>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 0.00602 in 213,395 control chromosomes in the GnomAD database, including 6 homozygotes. There are 379 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0051 ( 3 hom., 156 hem., cov: 23)
Exomes 𝑓: 0.0070 ( 3 hom. 223 hem. )
Consequence
MECP2
NM_001110792.2 3_prime_UTR
NM_001110792.2 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.618
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 Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
Variant X-154029878-C-G is Benign according to our data. Variant chrX-154029878-C-G is described in ClinVar as [Benign]. Clinvar id is 143273.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154029878-C-G is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00514 (578/112347) while in subpopulation NFE AF= 0.00764 (406/53167). AF 95% confidence interval is 0.00702. There are 3 homozygotes in gnomad4. There are 156 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MECP2 | NM_001110792.2 | c.*489G>C | 3_prime_UTR_variant | 3/3 | ENST00000453960.7 | ||
MECP2 | NM_004992.4 | c.*489G>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.*489G>C | 3_prime_UTR_variant | 4/4 | 1 | NM_004992.4 | P1 | ||
MECP2 | ENST00000453960.7 | c.*489G>C | 3_prime_UTR_variant | 3/3 | 1 | NM_001110792.2 |
Frequencies
GnomAD3 genomes AF: 0.00514 AC: 577AN: 112295Hom.: 2 Cov.: 23 AF XY: 0.00453 AC XY: 156AN XY: 34441
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GnomAD4 exome AF: 0.00700 AC: 707AN: 101048Hom.: 3 Cov.: 0 AF XY: 0.00724 AC XY: 223AN XY: 30790
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GnomAD4 genome AF: 0.00514 AC: 578AN: 112347Hom.: 3 Cov.: 23 AF XY: 0.00452 AC XY: 156AN XY: 34503
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ClinVar
Significance: 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 | Nov 01, 2007 | - - |
Rett syndrome Benign:1
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 Specifications to the ACMG/AMP Variant Interpretation Guidelines VCEP 2.0, 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 2.0 (BA1). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at