rs375421208
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_022552.5(DNMT3A):c.1491T>C(p.Cys497=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,904 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
DNMT3A
NM_022552.5 synonymous
NM_022552.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.488
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 2-25245316-A-G is Benign according to our data. Variant chr2-25245316-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 434952.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=0.488 with no splicing effect.
BS2
?
High AC in GnomAd at 18 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNMT3A | NM_022552.5 | c.1491T>C | p.Cys497= | synonymous_variant | 13/23 | ENST00000321117.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNMT3A | ENST00000321117.10 | c.1491T>C | p.Cys497= | synonymous_variant | 13/23 | 1 | NM_022552.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000118 AC: 18AN: 152188Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
18
AN:
152188
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000320 AC: 8AN: 249988Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 134962
GnomAD3 exomes
AF:
AC:
8
AN:
249988
Hom.:
AF XY:
AC XY:
4
AN XY:
134962
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461598Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727074
GnomAD4 exome
AF:
AC:
10
AN:
1461598
Hom.:
Cov.:
31
AF XY:
AC XY:
3
AN XY:
727074
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152306Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5AN XY: 74482
GnomAD4 genome
?
AF:
AC:
17
AN:
152306
Hom.:
Cov.:
33
AF XY:
AC XY:
5
AN XY:
74482
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1
AN:
3478
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 30, 2017 | - - |
DNMT3A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 08, 2022 | 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 | Dec 11, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at