Back
LYFE SCIENCES
Project: HERA
NM_000051.3:c.3118A>G
p.Met1040Val  ·  ATM
Starting
Initialising…
0%
Legacy Engine
Ready
View Legacy →
Classification rationale
1

The ATM c.3118A>G (p.Met1040Val) variant has been observed in somatic cancers 4 times in COSMIC and is reported in ClinVar as Benign with expert panel review.

clinvar ↗
2

This variant is common in population databases, with gnomAD v4.1 showing an overall allele frequency of 0.20969% and an African/African American allele frequency of 3.97073%, which exceeds the ATM BA1 threshold of 0.5% grpmax filtering allele frequency.

gnomad_v4 ↗ gnomad_v2 ↗ cspec ↗
3

Computational evidence supports a benign effect, with REVEL 0.096, BayesDel -0.451498, and SpliceAI maximum delta score 0.01, meeting the ATM BP4 thresholds and not meeting PP3 thresholds.

spliceai ↗ cspec ↗
Applied criteria
Met
Not met
Not assessed
N/A
Very strong
Strong
Moderate
Supporting
Pathogenic evidence
PVS
PVS1
PS
PS1
PS2
PS3
PS4
PM
PM1
PM2
PM3
PM4
PM5
PM6
PP
PP1
PP2
PP3
PP4
PP5
Benign evidence
BA
BA1
BS
BS1
BS2
BS3
BS4
BP
BP1
BP2
BP3
BP4
BP5
BP6
BP7
PVS1
—
—
Rationale
Select a criterion to inspect its explanation.
Evidence used
  • —
Gaps remaining
  • —
Rule
—
Publications
—
Research and evidence
gnomAD v2.1 evidence
v2.1
gnomAD v4.1 evidence
v4.1
01
Population
gnomAD v2.1This variant is present in gnomAD v2.1 (AF= 0.00399369; MAF= 0.39937%, 1129/282696 alleles, homozygotes = 26) and has highest observed frequency in the African/African American population (AF= 0.0418838; MAF= 4.18838%, 1045/24950 alleles, homozygotes = 26); grpmax FAF= 0.0399312.
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 0.00209693; MAF= 0.20969%, 3384/1613784 alleles, homozygotes = 67) and has highest observed frequency in the African/African American population (AF= 0.0397073; MAF= 3.97073%, 2979/75024 alleles, homozygotes = 67); grpmax FAF= 0.0385176.
gnomAD v2 ↗ gnomAD v4 ↗
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Benign (22 clinical laboratories) and as Likely benign (5 clinical laboratories) and as benign (1 clinical laboratory) and as Benign by ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel, ClinGen (expert panel). (ClinVarID = 3027)
ClinVar ↗
Functional evidence
03
Functional
OncoKB: Unknown Oncogenic Effect
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. ATM, a kinase involved in the DNA damage response, is mutated in various solid and hematologic malignancies.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.096. BayesDel score = -0.451498.
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV53737085, n = 4 times).
COSMIC ↗
Cancer hotspots evidence
06
Cancer hotspots Not found
This variant does not lie in a statistically significant hotspot.
ResidueM1040
Hotspots ↗