Genetic Information
Gene & Transcript Details
| ID | Status | Details |
|---|---|---|
| NM_033360.2 | Alternative | 5436 nt | 182–751 |
| NM_033360.4 | Alternative | 5430 nt | 191–760 |
| NM_033360.3 | Alternative | 5889 nt | 193–762 |
Variant Details
Clinical & Population Data
Population Frequency
gnomADClinVar
Open"This variant has been reported in ClinVar as Likely benign (1 clinical laboratories)."
COSMIC Somatic Evidence
Open
Functional Impact & Domains
Functional Domain
Computational Analysis
Pathogenicity Predictions
SpliceAISpliceAI Scores
Window: ±500bp| Effect Type | Score | Position |
|---|---|---|
| Acceptor Loss (AL) | 0.0 | 45 bp |
| Donor Loss (DL) | 0.0 | 214 bp |
| Acceptor Gain (AG) | 0.02 | -33 bp |
| Donor Gain (DG) | 0.0 | 12 bp |
VCEP Guidelines
Applied ACMG/AMP Criteria (VCEP Specific)
PVS1 (Not Applied)
According to standard ACMG guidelines, the PVS1 rule: a null variant (nonsense, frameshift, canonical ±1 or 2 splice sites, initiation codon, single or multiexon deletion) in a gene where loss of function is a known mechanism of disease. The evidence for this variant shows it is a synonymous (silent) change with no alteration to protein sequence. Therefore, this criterion is not applied.
PS1 (Not Applied)
According to VCEP guidelines, the PS1 rule (Strong): same amino acid change as a previously established pathogenic variant regardless of nucleotide change. The evidence for this variant shows no amino acid change (V112=). Therefore, this criterion is not applied.
PS2 (Not Applied)
According to VCEP guidelines, the PS2 rule (Very Strong/Strong/Moderate) applies to confirmed or assumed de novo variants. The evidence for this variant shows no available de novo inheritance data. Therefore, this criterion is not applied.
PS3 (Not Applied)
According to VCEP guidelines, the PS3 rule (Moderate/Supporting) requires well-validated functional studies demonstrating a damaging effect. The evidence for this variant shows no functional characterization. Therefore, this criterion is not applied.
PS4 (Not Applied)
According to VCEP guidelines, the PS4 rule (Strong/Moderate/Supporting) requires statistical evidence of enrichment in affected individuals. The evidence for this variant shows no case-control or cohort data. Therefore, this criterion is not applied.
PM1 (Not Applied)
According to VCEP guidelines, the PM1 rule (Moderate) applies to variants in critical functional domains (P-loop AA10-17, SW1 AA25-40, SW2 AA57-64, SAK AA145-156). The evidence for this variant at amino acid 112 lies outside these regions. Therefore, this criterion is not applied.
PM2 (Supporting)
According to VCEP guidelines, the PM2 rule (Supporting): variant must be absent from controls (gnomAD). The evidence for this variant shows absence from gnomAD and other population databases. Therefore, this criterion is applied at Supporting strength.
PM3 (Not Applied)
According to standard ACMG guidelines, the PM3 rule (Moderate) applies to recessive conditions requiring phase-confirmed observations in trans. The evidence for this variant shows no relevant recessive inheritance context. Therefore, this criterion is not applied.
PM4 (Not Applied)
According to VCEP guidelines, the PM4 rule (Moderate) applies to in-frame insertions/deletions or stop-loss variants. The evidence for this variant shows a synonymous change. Therefore, this criterion is not applied.
PM5 (Not Applied)
According to VCEP guidelines, the PM5 rule (Strong/Moderate) applies to novel missense changes at codons with established pathogenic missense changes. The evidence for this variant shows no amino acid change. Therefore, this criterion is not applied.
PM6 (Not Applied)
According to VCEP guidelines, the PM6 rule (Strong/Moderate/Supporting) applies to assumed de novo variants without confirmation. The evidence for this variant shows no inheritance data. Therefore, this criterion is not applied.
PP1 (Not Applied)
According to VCEP guidelines, the PP1 rule (Supporting/Moderate/Strong) requires segregation of the variant with disease in multiple affected family members. The evidence for this variant shows no family segregation data. Therefore, this criterion is not applied.
PP2 (Not Applied)
According to standard ACMG guidelines, the PP2 rule (Supporting) applies to missense variants in genes with low rate of benign missense variation. The evidence for this variant shows it is synonymous. Therefore, this criterion is not applied.
PP3 (Not Applied)
According to VCEP guidelines, the PP3 rule (Supporting) applies to missense variants with REVEL ≥0.7 or impactful splicing predictions. The evidence for this variant shows neither missense effect nor significant splicing impact. Therefore, this criterion is not applied.
PP4 (Not Applied)
According to standard ACMG guidelines, the PP4 rule (Supporting) requires a highly specific phenotype or family history. The evidence for this variant shows no phenotype data. Therefore, this criterion is not applied.
PP5 (Not Applied)
According to standard ACMG guidelines, the PP5 rule (Supporting) applies when a reputable source reports a variant as pathogenic but evidence is unavailable. The evidence for this variant shows a reputable source reporting likely benign (ClinVar), not pathogenic. Therefore, this criterion is not applied.
BA1 (Not Applied)
According to VCEP guidelines, the BA1 rule (Stand Alone) requires allele frequency ≥0.05% in gnomAD. The evidence for this variant shows absence in population databases. Therefore, this criterion is not applied.
BS1 (Not Applied)
According to VCEP guidelines, the BS1 rule (Strong) requires allele frequency ≥0.025% in gnomAD. The evidence for this variant shows absence in population databases. Therefore, this criterion is not applied.
BS2 (Not Applied)
According to VCEP guidelines, the BS2 rule (Strong/Supporting) applies when observed in healthy adult individuals. The evidence for this variant shows no such observations. Therefore, this criterion is not applied.
BS3 (Not Applied)
According to standard ACMG guidelines, the BS3 rule (Strong) requires well-validated functional studies showing no damaging effect. The evidence for this variant shows no functional studies. Therefore, this criterion is not applied.
BS4 (Not Applied)
According to standard ACMG guidelines, the BS4 rule (Strong) applies when there is lack of segregation in affected members of a family. The evidence for this variant shows no segregation data. Therefore, this criterion is not applied.
BP1 (Not Applied)
According to VCEP guidelines, the BP1 rule (Supporting) applies to truncating variants in genes without LOF correlation. The evidence for this variant shows a synonymous change. Therefore, this criterion is not applied.
BP2 (Not Applied)
According to standard ACMG guidelines, the BP2 rule (Supporting/Moderate/Strong) applies when observed in trans with a pathogenic variant for a dominant disorder or cis for a recessive disorder. The evidence for this variant shows no such data. Therefore, this criterion is not applied.
BP3 (Not Applied)
According to standard ACMG guidelines, the BP3 rule (Supporting) applies to in-frame indels in repetitive regions. The evidence for this variant shows a single-nucleotide substitution. Therefore, this criterion is not applied.
BP4 (Not Applied)
According to VCEP guidelines, the BP4 rule (Supporting) is specific to missense variants with REVEL ≤0.3. The evidence for this variant shows a synonymous change. Therefore, this criterion is not applied.
BP5 (Not Applied)
According to standard ACMG guidelines, the BP5 rule (Supporting/Moderate/Strong) applies when a variant is found in a case with an alternate molecular basis for disease. The evidence for this variant shows none. Therefore, this criterion is not applied.
BP6 (Supporting)
According to standard ACMG guidelines, the BP6 rule (Supporting): reputable source reports variant as benign but evidence unavailable. The evidence for this variant shows ClinVar reports it as Likely Benign with no underlying data. Therefore, this criterion is applied at Supporting strength.
BP7 (Supporting)
According to standard ACMG guidelines, the BP7 rule (Supporting): a synonymous variant with no predicted splice impact and not highly conserved. The evidence for this variant shows SpliceAI predicts no splicing impact (score 0.02) and no amino acid change. Therefore, this criterion is applied at Supporting strength.