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LYFE SCIENCES
Project: HERA
NM_022552.4:c.1475-19C>T
p.?  ·  DNMT3A
ACMG/AMP
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Classification rationale
1

The DNMT3A c.1475-19C>T (p.?) variant has been reported in ClinVar with a Likely benign classification from a single clinical laboratory.

clinvar ↗
2

This variant is present at very low overall frequency in population databases, with gnomAD v2.1 AF 0.00081% (2/247888 alleles) and gnomAD v4.1 AF 0.00043% (7/1611438 alleles); the highest observed frequency is 0.04936% in the Middle Eastern population in gnomAD v4.1, which is below the default BS1 threshold of 0.3% and below the BA1 threshold of 1.0%.

gnomad_v2 ↗ gnomad_v4 ↗
3

SpliceAI predicts no significant splice impact for this variant, with a maximum delta score of 0.00, which supports a benign computational interpretation rather than evidence for abnormal splicing.

spliceai ↗
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
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Rationale
Select a criterion to inspect its explanation.
Evidence used
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Gaps remaining
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Rule
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Publications
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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= 8.06816e-06; MAF= 0.00081%, 2/247888 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 3.30535e-05; MAF= 0.00331%, 1/30254 alleles, homozygotes = 0).
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 4.34395e-06; MAF= 0.00043%, 7/1611438 alleles, homozygotes = 0) and has highest observed frequency in the Middle Eastern population (AF= 0.000493583; MAF= 0.04936%, 3/6078 alleles, homozygotes = 0); grpmax FAF= 0.00013368.
gnomAD v2 ↗ gnomAD v4 ↗
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Likely benign (1 clinical laboratory).
ClinVar ↗
03
Functional
No functional summary recorded.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant has not previously been reported in somatic cancers (COSMIC).
COSMIC ↗
06
Cancer hotspots
No cancer hotspot summary recorded.