Genetic Information
Gene & Transcript Details
| ID | Status | Details |
|---|---|---|
| NM_000051.3 | RefSeq Select | 13147 nt | 386–9556 |
| NM_000051.4 | MANE Select | 12915 nt | 151–9321 |
Variant Details
Clinical & Population Data
Population Frequency
gnomADClinVar
Open"This variant has been reported in ClinVar as Likely benign (1 clinical laboratories) and as 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 | -88 bp |
| Donor Loss (DL) | 0.01 | -369 bp |
| Acceptor Gain (AG) | 0.02 | 88 bp |
| Donor Gain (DG) | 0.0 | 228 bp |
VCEP Guidelines
Applied ACMG/AMP Criteria (VCEP Specific)
PVS1 (Not Applied)
According to VCEP guidelines, the rule for PVS1 is: "Use ATM PVS1 Decision Tree". The evidence for this variant shows: c.3153+20delT is a deep intronic variant outside the consensus splice sites without any demonstrated impact on splicing. Therefore, this criterion is not applied.
PS1 (Not Applied)
According to standard ACMG guidelines, the rule for PS1 is: "Same amino acid change as a known pathogenic variant". The evidence for this variant shows: no amino acid change (intronic). Therefore, this criterion is not applied.
PS2 (Not Applied)
According to standard ACMG guidelines, the rule for PS2 is: "De novo (both maternity and paternity confirmed)". The evidence for this variant shows: no de novo data available. Therefore, this criterion is not applied.
PS3 (Not Applied)
According to VCEP guidelines, the rule for PS3 is: "Use ATM PS3 Decision Tree; functional assays showing failure to rescue ATM-specific features". The evidence for this variant shows: no functional characterization reported. Therefore, this criterion is not applied.
PS4 (Not Applied)
According to standard ACMG guidelines, the rule for PS4 is: "Prevalence in affected individuals significantly increased compared to controls". The evidence for this variant shows: no case-control or cohort data. Therefore, this criterion is not applied.
PM1 (Not Applied)
According to standard ACMG guidelines, the rule for PM1 is: "Located in a mutational hot spot or well‐studied functional domain". The evidence for this variant shows: intronic region without known functional domain. Therefore, this criterion is not applied.
PM2 (Supporting)
According to VCEP guidelines, the rule for PM2 is: "Supporting Strength: Frequency ≤.001% if n=1 in a single sub population". The evidence for this variant shows: absent from gnomAD (0/251092 alleles). Therefore, this criterion is applied at Supporting strength because the variant is sufficiently rare.
PM3 (Not Applied)
According to VCEP guidelines, the rule for PM3 is: "Use ATM PM3/BP2 table for recessive cases". The evidence for this variant shows: no evidence of trans configuration with a pathogenic variant in recessive disease context. Therefore, this criterion is not applied.
PM4 (Not Applied)
According to standard ACMG guidelines, the rule for PM4 is: "Protein length changes due to in‐frame deletions/insertions". The evidence for this variant shows: intronic deletion not affecting coding frame. Therefore, this criterion is not applied.
PM5 (Not Applied)
According to standard ACMG guidelines, the rule for PM5 is: "Novel missense change at an amino acid residue where a different pathogenic missense change has been seen". The evidence for this variant shows: no missense change. Therefore, this criterion is not applied.
PM6 (Not Applied)
According to standard ACMG guidelines, the rule for PM6 is: "Assumed de novo, but without confirmation of paternity/maternity". The evidence for this variant shows: no de novo data. Therefore, this criterion is not applied.
PP1 (Not Applied)
According to standard ACMG guidelines, the rule for PP1 is: "Co‐segregation with disease in multiple affected family members". The evidence for this variant shows: no segregation data. Therefore, this criterion is not applied.
PP2 (Not Applied)
According to standard ACMG guidelines, the rule for PP2 is: "Missense variant in a gene with low rate of benign missense variation". The evidence for this variant shows: not a missense variant. Therefore, this criterion is not applied.
PP3 (Not Applied)
According to VCEP guidelines, the rule for PP3 is: "Supporting if REVEL >.7333 or splicing predictor shows impact". The evidence for this variant shows: SpliceAI score 0.02, no predicted splicing impact. Therefore, this criterion is not applied.
PP4 (Not Applied)
According to standard ACMG guidelines, the rule for PP4 is: "Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology". The evidence for this variant shows: no phenotype data. Therefore, this criterion is not applied.
PP5 (Not Applied)
According to standard ACMG guidelines, the rule for PP5 is: "Reputable source reports variant as pathogenic". The evidence for this variant shows: no reputable source reports pathogenic. Therefore, this criterion is not applied.
BA1 (Not Applied)
According to VCEP guidelines, the rule for BA1 is: "Stand Alone Filtering Allele Frequency >.5%". The evidence for this variant shows: allele frequency =0%. Therefore, this criterion is not applied.
BS1 (Not Applied)
According to VCEP guidelines, the rule for BS1 is: "Strong Filtering Allele Frequency >.05%". The evidence for this variant shows: allele frequency =0%. Therefore, this criterion is not applied.
BS2 (Not Applied)
According to standard ACMG guidelines, the rule for BS2 is: "Observed in a healthy adult individual for a recessive disorder". The evidence for this variant shows: no data in healthy individuals. Therefore, this criterion is not applied.
BS3 (Not Applied)
According to VCEP guidelines, the rule for BS3 is: "Use when variant rescues ATM-specific features in functional assays". The evidence for this variant shows: no functional rescue data. Therefore, this criterion is not applied.
BS4 (Not Applied)
According to standard ACMG guidelines, the rule for BS4 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 standard ACMG guidelines, the rule for BP1 is: "Missense variant in a gene where only truncating variants cause disease". The evidence for this variant shows: not a missense variant. Therefore, this criterion is not applied.
BP2 (Not Applied)
According to VCEP guidelines, the rule for BP2 is: "Use ATM PM3/BP2 table for observations in trans with pathogenic variants". The evidence for this variant shows: no such observations. Therefore, this criterion is not applied.
BP3 (Not Applied)
According to standard ACMG guidelines, the rule for BP3 is: "In‐frame deletions/insertions in repetitive region without known function". The evidence for this variant shows: not an in‐frame indel in a repetitive region. Therefore, this criterion is not applied.
BP4 (Not Applied)
According to VCEP guidelines, the rule for BP4 is: "Supporting if REVEL ≤.249 or splicing predictor shows no impact". The evidence for this variant shows: SpliceAI score 0.02 but variant qualifies for BP7 as deep intronic; BP4 and BP7 should not be used together. Therefore, this criterion is not applied.
BP5 (Not Applied)
According to standard ACMG guidelines, the rule for BP5 is: "Variant found in a case with an alternate molecular basis for disease". The evidence for this variant shows: no such data. Therefore, this criterion is not applied.
BP6 (Supporting)
According to standard ACMG guidelines, the rule for BP6 is: "Reputable source reports variant as benign". The evidence for this variant shows: ClinVar entries from two clinical laboratories reporting Likely benign/Benign. Therefore, this criterion is applied at Supporting strength.
BP7 (Supporting)
According to VCEP guidelines, the rule for BP7 is: "Supporting Can be considered for synonymous and deep intronic variants defined as further than (but not including) +7 at donor sites". The evidence for this variant shows: c.3153+20delT is located 20 bases into the intron, with no predicted splicing impact. Therefore, this criterion is applied at Supporting strength.