Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_001100.4(ACTA1):c.1104C>T (p.Gly368=)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA1442705

381474 (ClinVar)

Gene: ACTA1

Condition: alpha-actinopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: a9f7e1f2-292c-443e-a618-d0e947f53c99

Approved on: 2024-08-27

Published on: 2024-12-16

HGVS expressions

NM_001100.4:c.1104C>T

NM_001100.4(ACTA1):c.1104C>T (p.Gly368=)

NC_000001.11:g.229431529G>A

CM000663.2:g.229431529G>A

NC_000001.10:g.229567276G>A

CM000663.1:g.229567276G>A

NC_000001.9:g.227633899G>A

NG_006672.1:g.7568C>T

ENST00000366683.4:c.1026C>T

ENST00000684723.1:c.969C>T

ENST00000366683.3:c.735C>T

ENST00000366684.7:c.1104C>T

NM_001100.3:c.1104C>T

Likely Benign

BP7 BP4

PM2 BA1 BS1

Evidence Links 0

Expert Panel

Congenital Myopathies VCEP

Criteria Specification Information

Criteria Specification: ClinGen Congenital Myopathies Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ACTA1 Version 2.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Congenital Myopathies VCEP

The variant NM_001100.4:c.1104C>T in ACTA1 is a synonymous (silent) variant (p.Gly368=). The highest population filtering allele frequency in gnomAD v4.1.0 is 0.000006150 (13/1180024) in the European (non-Finnish) population(no population codes met). However, SpliceAI predicted no impact on splicing, meeting BP4/BP7 criteria. In summary, the variant meets criteria to be classified as likely benign for autosomal dominant alpha-actinopathy. ACMG/AMP criteria met, as specified by the congenital myopathies VCEP: BP4, BP7 (ClinGen Congenital Myopathies VCEP specifications version 2; 08/27/2024).

BP7

SpliceAI scores of 0 for donor and acceptor loss and donor and acceptor gain, indicating there is no predicted impact on splicing.

BP4

SpliceAI scores of 0 for donor and acceptor loss and donor and acceptor gain, indicating there is no predicted impact on splicing.

PM2

The highest population filtering allele frequency in gnomAD v4.1.0 is 0.000006150 (13/1180024) in the European (non-Finnish) population(no population codes met).

BA1

The highest population filtering allele frequency in gnomAD v4.1.0 is 0.000006150 (13/1180024) in the European (non-Finnish) population(no population codes met).

BS1

The highest population filtering allele frequency in gnomAD v4.1.0 is 0.000006150 (13/1180024) in the European (non-Finnish) population(no population codes met).

Curation History

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