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_001100.4(ACTA1):c.36C>T (p.Cys12=)

CA38817036

511235 (ClinVar)

Gene: ACTA1
Condition: alpha-actinopathy
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: ec520a2b-3add-46da-9396-a7fd668624ab
Approved on: 2024-08-27
Published on: 2024-12-16

HGVS expressions

NM_001100.4:c.36C>T
NM_001100.4(ACTA1):c.36C>T (p.Cys12=)
NC_000001.11:g.229433080G>A
CM000663.2:g.229433080G>A
NC_000001.10:g.229568827G>A
CM000663.1:g.229568827G>A
NC_000001.9:g.227635450G>A
NG_006672.1:g.6017C>T
ENST00000366683.4:c.36C>T
ENST00000684723.1:c.-6-200C>T
ENST00000366683.3:c.36C>T
ENST00000366684.7:c.36C>T
NM_001100.3:c.36C>T
More

Likely Benign

Met criteria codes 2
BP7 BP4
Not Met criteria codes 24
PS1 PS3 PS2 PS4 PP4 PP1 PP3 PP2 PM6 PM2 PM5 PM1 PM4 PM3 PVS1 BA1 BS2 BS3 BS4 BS1 BP5 BP3 BP2 BP1

Evidence Links 0

Expert Panel

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.36C>T is a synonymous (silent) variant (p.Cys12=) in exon 2/7. The highest population minor allele frequency in gnomAD v4.1.0 is 0.000002478 (3/1180002 alleles) in European (non-Finnish) population (no population codes met). This silent variant is not predicted to impact splicing by SpliceAI. In addition, it occurs at a nucleotide that is poorly conserved as shown by the UCSC Genome Browser (BP4, BP7). 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 ClinGen Congenital Myopathies VCEP: BP4, BP7 (ClinGen Congenital Myopathies VCEP specifications version 2; 08/27/2024).
Met criteria codes
BP7
The c.36C>T (p.Cys12=) variant is a synonymous (silent) variant that is not predicted by SpliceAI to impact splicing. It occurs at a nucleotide that is poorly conserved as shown by UCSC.
BP4
The c.36C>T (p.Cys12=) variant is a synonymous (silent) variant that is not predicted by SpliceAI to impact splicing.
Not Met criteria codes
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
SpliceAI predicts no impact
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
The highest population minor allele frequency in gnomAD v4.1.0 is 0.000002478 (3/1180002 alleles) in European (non-Finnish) population (no population codes met).
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
The highest population minor allele frequency in gnomAD v4.1.0 is 0.000002478 (3/1180002 alleles) in European (non-Finnish) population (no population codes met).
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
The highest population minor allele frequency in gnomAD v4.1.0 is 0.000002478 (3/1180002 alleles) in European (non-Finnish) population (no population codes met).
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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