chrX-154031267-G-T
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001110792.2(MECP2):c.597C>A(p.Gly199=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,210,600 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )
Consequence
MECP2
NM_001110792.2 synonymous
NM_001110792.2 synonymous
Scores
3
9
Clinical Significance
Conservation
PhyloP100: -0.782
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 -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05198136).
BP6
Variant X-154031267-G-T is Benign according to our data. Variant chrX-154031267-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 413766.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.782 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MECP2 | NM_001110792.2 | c.597C>A | p.Gly199= | synonymous_variant | 3/3 | ENST00000453960.7 | |
MECP2 | NM_004992.4 | c.561C>A | p.Gly187= | synonymous_variant | 4/4 | ENST00000303391.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MECP2 | ENST00000453960.7 | c.597C>A | p.Gly199= | synonymous_variant | 3/3 | 1 | NM_001110792.2 | ||
MECP2 | ENST00000303391.11 | c.561C>A | p.Gly187= | synonymous_variant | 4/4 | 1 | NM_004992.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000890 AC: 1AN: 112312Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34458
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GnomAD3 exomes AF: 0.00000546 AC: 1AN: 183244Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67746
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GnomAD4 exome AF: 0.00000182 AC: 2AN: 1098234Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 1AN XY: 363590
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GnomAD4 genome AF: 0.00000890 AC: 1AN: 112366Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34522
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Severe neonatal-onset encephalopathy with microcephaly Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;N
REVEL
Benign
Sift4G
Uncertain
D;D
Vest4
MutPred
Gain of solvent accessibility (P = 0.0354);.;
MVP
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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