Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_001110792.2(MECP2):c.474C>T (p.Gly158=)

CA232966

143574 (ClinVar)

Gene: MECP2
Condition: Rett syndrome
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: 2b2c3166-7dd2-4132-bd80-c73c165c5682
Approved on: 2025-10-28
Published on: 2025-12-23

HGVS expressions

NM_001110792.2:c.474C>T
NM_001110792.2(MECP2):c.474C>T (p.Gly158=)
NC_000023.11:g.154031390G>A
CM000685.2:g.154031390G>A
NC_000023.10:g.153296841G>A
CM000685.1:g.153296841G>A
NC_000023.9:g.152950035G>A
NG_007107.2:g.110738C>T
NG_007107.3:g.110714C>T
ENST00000303391.11:c.438C>T
ENST00000453960.7:c.474C>T
ENST00000637917.1:c.65+6C>T
ENST00000303391.10:c.438C>T
ENST00000369957.5:c.*492C>T
ENST00000407218.5:c.468+6C>T
ENST00000453960.6:c.474C>T
ENST00000486506.5:n.2786C>T
ENST00000611468.1:c.426C>T
ENST00000619732.4:c.438C>T
ENST00000622433.4:c.426C>T
ENST00000628176.2:c.432+6C>T
NM_001110792.1:c.474C>T
NM_001316337.1:c.159C>T
NM_004992.3:c.438C>T
NM_001316337.2:c.159C>T
NM_001369391.2:c.159C>T
NM_001369392.2:c.159C>T
NM_001369393.2:c.159C>T
NM_001369394.1:c.159C>T
NM_001369394.2:c.159C>T
NM_001386137.1:c.-129+6C>T
NM_001386138.1:c.-129+6C>T
NM_001386139.1:c.-129+6C>T
NM_004992.4:c.438C>T
More

Benign

Met criteria codes 4
BP5 PP3 BS2 BS1
Not Met criteria codes 1
PM2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Rett and Angelman-like Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MECP2 Version 5.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Rett and Angelman-like Disorders VCEP
The highest population minor allele frequency of the c.438C>T (p.Gly146=) variant in MECP2 (NM_004992.4) in gnomAD v4.1.0 is 0.00006432 in the European (Finnish) population, which is higher than the ClinGen Rett and Angelman-like Disorders VCEP threshold (≥0.0000083) for BS1, and therefore meets this criterion (BS1). The p.Gly146= variant is observed in at least 2 unaffected individuals (internal database - LabCorp (formerly Invitae); internal database - Ambry) (BS2). The p.Gly146= variant is found in a patient with an alternate molecular basis of disease (internal database - Labcorp (formerly Invitae)) (BP5). The computational splicing predictor SpliceAI gives a score of 0.33 for donor gain, predicting that the variant creates a cryptic splice donor site in exon 4 of MECP2 (PP3). The ClinGen Rett and Angelman-like Disorders VCEP classified this variant as benign based on BS1, BS2, and BP5. (MECP2 Specifications v5.0; curation approved on 10/28/2025)
Met criteria codes
BP5
The p.Gly146= variant (NM_004992.4) is found in a patient with an alternate molecular basis of disease (internal database - Labcorp (formerly Invitae)) (BP5).
PP3
The computational splicing predictor SpliceAI gives a score of 0.33 for donor gain, predicting that the variant creates a cryptic splice donor site in exon 4 of MECP2 (PP3).
BS2
The p.Gly146= variant (NM_004992.4) is observed in at least 2 unaffected individuals (internal database - LabCorp (formerly Invitae); internal database - Ambry) (BS2).
BS1
The highest population minor allele frequency of the p.Gly146= variant in MECP2 (NM_004992.4) in gnomAD v4.1.0 is 0.00006432 in the European (Finnish) population, which is higher than the ClinGen Rett and Angelman-like Disorders VCEP threshold (≥0.0000083) for BS1, and therefore meets this criterion (BS1).
Not Met criteria codes
PM2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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