Variant 2-25246759-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022552.5(DNMT3A):c.1140G>A(p.Ala380Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00303 in 1,613,582 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 61 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 53 hom. )

Consequence

DNMT3A
NM_022552.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -6.13

Variant links:

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]

DNMT3A links:

DNMT3A (HGNC:):

DNMT3A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 2-25246759-C-T is Benign according to our data. Variant chr2-25246759-C-T is described in ClinVar as [Benign]. Clinvar id is 475175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.13 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNMT3A	NM_022552.5 linkuse as main transcript	c.1140G>A	p.Ala380Ala	synonymous_variant	10/23	ENST00000321117.10	NP_072046.2	Q9Y6K1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNMT3A	ENST00000321117.10 linkuse as main transcript	c.1140G>A	p.Ala380Ala	synonymous_variant	10/23	1	NM_022552.5	ENSP00000324375.5		Q9Y6K1-1

Frequencies

GnomAD3 genomes

AF:

0.0154

AC:

2341

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0523

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00844

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00447

AC:

1116

AN:

249870

Hom.:

AF XY:

0.00347

AC XY:

470

AN XY:

135328

show subpopulations

Gnomad AFR exome

AF:

0.0550

Gnomad AMR exome

AF:

0.00446

Gnomad ASJ exome

AF:

0.00150

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000381

Gnomad OTH exome

AF:

0.00295

GnomAD4 exome

AF:

0.00173

AC:

2534

AN:

1461268

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

1122

AN XY:

726980

show subpopulations

Gnomad4 AFR exome

AF:

0.0526

Gnomad4 AMR exome

AF:

0.00458

Gnomad4 ASJ exome

AF:

0.00180

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000243

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000189

Gnomad4 OTH exome

AF:

0.00434

GnomAD4 genome

AF:

0.0154

AC:

2350

AN:

152314

Hom.:

Cov.:

AF XY:

0.0147

AC XY:

1094

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0524

Gnomad4 AMR

AF:

0.00843

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00680

Hom.:

Bravo

AF:

0.0178

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 17, 2018	- -

Tatton-Brown-Rahman overgrowth syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.0030

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over