Submissions for variant NM_001110792.2(MECP2):c.429C>G (p.Ala143=)

gnomAD frequency: 0.00018  dbSNP: rs61748385

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV001800453	SCV002047356	benign	Rett syndrome	2021-10-26	reviewed by expert panel	curation	The allele frequency of the c.393C>G (p.Ala131=) variant in MECP2 (NM_004992.3) is 0.1698% in the Ashkenazi Jewish sub population in gnomAD, which is high enough to be classified as benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BA1). The silent c.393C>G (p.Ala131=) variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide (BP4, BP7). In summary, the c.393C>G (p.Ala131=) variant in MECP2 is classified as Benign based on the ACMG/AMP criteria (BA1, BP4, BP7).
Genetic Services Laboratory, University of Chicago	RCV000133090	SCV000247966	likely benign	not specified	2013-02-08	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000415752	SCV000493381	uncertain significance	not provided	2016-08-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000415752	SCV000513558	likely benign	not provided	2019-08-05	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000721058	SCV000851943	likely benign	History of neurodevelopmental disorder	2013-08-14	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
Invitae	RCV001518782	SCV001727541	benign	Severe neonatal-onset encephalopathy with microcephaly	2022-10-31	criteria provided, single submitter	clinical testing
Centre for Population Genomics, CPG	RCV001800453	SCV004098793	benign	Rett syndrome	2023-08-14	criteria provided, single submitter	curation	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).
PreventionGenetics, part of Exact Sciences	RCV003945157	SCV004763351	likely benign	MECP2-related condition	2021-05-19	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
RettBASE	RCV000133090	SCV000188079	benign	not specified	2010-03-10	no assertion criteria provided	curation