rs758596753
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBS1BS2_Supporting
The NM_022552.5(DNMT3A):c.72+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000613 in 1,549,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000042 ( 0 hom. )
Consequence
DNMT3A
NM_022552.5 intron
NM_022552.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0570
Genes affected
DNMT3A (HGNC:2978): (DNA methyltransferase 3 alpha) CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. Studies in mice have demonstrated that DNA methylation is required for mammalian development. This gene encodes a DNA methyltransferase that is thought to function in de novo methylation, rather than maintenance methylation. The protein localizes to the cytoplasm and nucleus and its expression is developmentally regulated. [provided by RefSeq, Mar 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 2-25313904-G-A is Benign according to our data. Variant chr2-25313904-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 434956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000243 (37/152230) while in subpopulation AMR AF= 0.00203 (31/15286). AF 95% confidence interval is 0.00147. There are 0 homozygotes in gnomad4. There are 23 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 37 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNMT3A | NM_022552.5 | c.72+9C>T | intron_variant | ENST00000321117.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNMT3A | ENST00000321117.10 | c.72+9C>T | intron_variant | 1 | NM_022552.5 | P3 | |||
DNMT3A | ENST00000264709.7 | c.72+9C>T | intron_variant | 1 | P3 | ||||
DNMT3A | ENST00000406659.3 | c.72+9C>T | intron_variant | 1 | |||||
DNMT3A | ENST00000380756.7 | c.72+9C>T | intron_variant, NMD_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000243 AC: 37AN: 152230Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000649 AC: 10AN: 154078Hom.: 0 AF XY: 0.0000369 AC XY: 3AN XY: 81390
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GnomAD4 exome AF: 0.0000415 AC: 58AN: 1396816Hom.: 0 Cov.: 30 AF XY: 0.0000334 AC XY: 23AN XY: 688974
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GnomAD4 genome ? AF: 0.000243 AC: 37AN: 152230Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23AN XY: 74372
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 18, 2016 | - - |
DNMT3A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 24, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Tatton-Brown-Rahman overgrowth syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at