rs61753973
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1
This summary comes from the ClinGen Evidence Repository: The allele frequency of the p.Ala439Ser variant in MECP2 (NM_004992.3) is 0.04208% in the African/African-American 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). In summary, the p.Ala439Ser variant in MECP2 is classified as Benign based on the ACMG/AMP criteria (BA1). LINK:https://erepo.genome.network/evrepo/ui/classification/CA222801/MONDO:0010726/036
Frequency
Consequence
NM_001110792.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MECP2 | NM_001110792.2 | c.1351G>T | p.Ala451Ser | missense_variant | 3/3 | ENST00000453960.7 | |
MECP2 | NM_004992.4 | c.1315G>T | p.Ala439Ser | missense_variant | 4/4 | ENST00000303391.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MECP2 | ENST00000453960.7 | c.1351G>T | p.Ala451Ser | missense_variant | 3/3 | 1 | NM_001110792.2 | ||
MECP2 | ENST00000303391.11 | c.1315G>T | p.Ala439Ser | missense_variant | 4/4 | 1 | NM_004992.4 | P1 | |
MECP2 | ENST00000628176.2 | c.*687G>T | 3_prime_UTR_variant | 5/5 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000897 AC: 10AN: 111438Hom.: 0 Cov.: 22 AF XY: 0.0000298 AC XY: 1AN XY: 33608
GnomAD3 exomes AF: 0.0000273 AC: 5AN: 183263Hom.: 0 AF XY: 0.0000295 AC XY: 2AN XY: 67729
GnomAD4 exome AF: 0.00000455 AC: 5AN: 1098163Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 2AN XY: 363525
GnomAD4 genome AF: 0.0000897 AC: 10AN: 111438Hom.: 0 Cov.: 22 AF XY: 0.0000298 AC XY: 1AN XY: 33608
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 14, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 09, 2013 | - - |
Severe neonatal-onset encephalopathy with microcephaly Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
Rett syndrome Benign:1
Benign, reviewed by expert panel | curation | ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel | Oct 11, 2022 | The allele frequency of the p.Ala439Ser variant in MECP2 (NM_004992.3) is 0.04208% in the African/African-American 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). In summary, the p.Ala439Ser variant in MECP2 is classified as Benign based on the ACMG/AMP criteria (BA1). - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 11, 2023 | This alteration is classified as likely 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