X-154030594-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001110792.2(MECP2):c.1270G>A(p.Val424Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,204,116 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 125 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001110792.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MECP2 | NM_001110792.2 | c.1270G>A | p.Val424Ile | missense_variant | 3/3 | ENST00000453960.7 | NP_001104262.1 | |
MECP2 | NM_004992.4 | c.1234G>A | p.Val412Ile | missense_variant | 4/4 | ENST00000303391.11 | NP_004983.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MECP2 | ENST00000453960.7 | c.1270G>A | p.Val424Ile | missense_variant | 3/3 | 1 | NM_001110792.2 | ENSP00000395535 | ||
MECP2 | ENST00000303391.11 | c.1234G>A | p.Val412Ile | missense_variant | 4/4 | 1 | NM_004992.4 | ENSP00000301948 | P1 | |
MECP2 | ENST00000628176.2 | c.*606G>A | 3_prime_UTR_variant | 5/5 | 3 | ENSP00000486978 | ||||
MECP2 | ENST00000407218.5 | downstream_gene_variant | 5 | ENSP00000384865 |
Frequencies
GnomAD3 genomes AF: 0.000147 AC: 16AN: 108662Hom.: 0 Cov.: 22 AF XY: 0.000129 AC XY: 4AN XY: 31064
GnomAD3 exomes AF: 0.000449 AC: 81AN: 180258Hom.: 0 AF XY: 0.000684 AC XY: 45AN XY: 65744
GnomAD4 exome AF: 0.000214 AC: 234AN: 1095409Hom.: 0 Cov.: 32 AF XY: 0.000335 AC XY: 121AN XY: 361687
GnomAD4 genome AF: 0.000147 AC: 16AN: 108707Hom.: 0 Cov.: 22 AF XY: 0.000129 AC XY: 4AN XY: 31119
ClinVar
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 07, 2017 | - - |
Benign, no assertion criteria provided | curation | RettBASE | Dec 05, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 16, 2016 | - - |
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 25, 2021 | This variant is associated with the following publications: (PMID: 12872250, 11055898, 24715477, 23810759) - |
Severe neonatal-onset encephalopathy with microcephaly Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
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). The variant is observed in at least 2 individuals with no features of Rett Syndrome (BS2). - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 17, 2017 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at