owencqueen/cgbench_data huggingface dataset:
Gene: ACTA1 (HGNC:129)
Evidence Code: PS3 — Moderate
Modification Type: Gene-specific
The two assays from PS3_Supporting may be stacked to reach a Moderate Strength
Gene: ACTA1 (HGNC:129)
Evidence Code: PS3 — Supporting
Modification Type: Gene-specific
Three specific assays are currently suggested to be applied at Supporting:




Actin Localization: An abnormal readout consists of integration of actin into cytoplasmic or intranuclear aggregates or rods.


Actin Polymerization: An abnormal readout consists of a significant reduction in levels of actin in insoluble fraction or absent or short polymerized actin filaments compared to WT.


Actin Motility Assay: An abnormal readout consists of percent motility, velocity, and force generation statistically different from WT.




If not listed above, it is acceptable to use PS3_Supporting for other functional analyses if




The assay has been validated by a known pathogenic and benign variant AND


There is plausible reason that the function the assay is testing relates to the phenotype AND


The assay conditions are likely to mimic the physiological environment.
Gene: ACTA1 (HGNC:129)
Evidence Code: PS4 — Strong
Modification Type: Gene-specific
8 case observations
Gene: ACTA1 (HGNC:129)
Evidence Code: PS4 — Moderate
Modification Type: Gene-specific
4 case observations
Gene: ACTA1 (HGNC:129)
Evidence Code: PS4 — Supporting
Modification Type: Gene-specific
2 case observations
Gene: ACTA1 (HGNC:129)
Evidence Code: PM2 — Supporting
Modification Type: Disease-specific,Gene-specific
PM2_Supporting may be applied if the minor allele frequency in population databases of at least 2000 alleles is 


absent (1 allele allowed) for autosomal dominant
Gene: ACTA1 (HGNC:129)
Evidence Code: PP2 — Supporting
Modification Type: Gene-specific
ACTA1 is a gene that is constrained for missense variation (gnomAD v4.1 z=6.09). PP2 may be used for missense variants with an autosomal dominant mode of inheritance.
Gene: ACTA1 (HGNC:129)
Evidence Code: PP4 — Strong
Modification Type: Disease-specific,Gene-specific
PP4 follows the published SVI guidance from Biesecker et al 2023 (PMID:38103548). For ACTA1, a conservative estimate of the diagnostic yield is 33%, which corresponds to +2 points and a moderate strength in Table 2 of this guidance. However, if the proband meets PP4_Moderate criteria and has had a comprehensive myopathy panel, exome, or genome testing that is negative for all other causes of myopathy, PP4 can be applied at strong, per the SVI guidance.   


The combination of PP1 and PP4 is capped at strong.
Gene: ACTA1 (HGNC:129)
Evidence Code: BA1 — Stand Alone
Modification Type: Gene-specific
The minor allele frequency using the filtering allele frequency of either exomes or genomes in gnomAD is 
≥0.0000781 for AD variants
. All continental populations in gnomAD used should have at least 2000 alleles and >1 observation.
Gene: ACTA1 (HGNC:129)
Evidence Code: BS1 — Strong
Modification Type: Gene-specific
The minor allele frequency using the filtering allele frequency of either exomes or genomes in gnomAD is 
≥0.00000781 for AD variants
. All continental populations used in gnomAD should have at least 2000 alleles and >1 observation.