chr20-32780142-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000201963.3(DNMT3B):c.27C>T(p.Ser9Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0643 in 1,613,566 control chromosomes in the GnomAD database, including 3,813 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.084 ( 654 hom., cov: 31)

Exomes 𝑓: 0.062 ( 3159 hom. )

Consequence

DNMT3B
ENST00000201963.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.388

Publications

14 publications found

Variant links:

Genes affected

DNMT3B (HGNC:2979): (DNA methyltransferase 3 beta) 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 which is thought to function in de novo methylation, rather than maintenance methylation. The protein localizes primarily to the nucleus and its expression is developmentally regulated. Mutations in this gene cause the immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome. Eight alternatively spliced transcript variants have been described. The full length sequences of variants 4 and 5 have not been determined. [provided by RefSeq, May 2011]

DNMT3B Gene-Disease associations (from GenCC):

immunodeficiency-centromeric instability-facial anomalies syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
facioscapulohumeral muscular dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
immunodeficiency-centromeric instability-facial anomalies syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DNMT3B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 20-32780142-C-T is Benign according to our data. Variant chr20-32780142-C-T is described in ClinVar as Benign. ClinVar VariationId is 402792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.388 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNMT3B	NM_006892.4 link	c.-6-176C>T		intron_variant	Intron 1 of 22	ENST00000328111.6	NP_008823.1	Q9UBC3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNMT3B	ENST00000328111.6 link	c.-6-176C>T		intron_variant	Intron 1 of 22	1	NM_006892.4	ENSP00000328547.2		Q9UBC3-1

Frequencies

GnomAD3 genomes

AF:

0.0844

AC:

12827

AN:

151962

Hom.:

652

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.0459

Gnomad ASJ

AF:

0.0801

Gnomad EAS

AF:

0.0717

Gnomad SAS

AF:

0.0744

Gnomad FIN

AF:

0.0701

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0594

Gnomad OTH

AF:

0.0689

GnomAD2 exomes

AF:

0.0654

AC:

16231

AN:

248260

AF XY:

0.0637

show subpopulations

Gnomad AFR exome

AF:

0.148

Gnomad AMR exome

AF:

0.0344

Gnomad ASJ exome

AF:

0.0745

Gnomad EAS exome

AF:

0.0727

Gnomad FIN exome

AF:

0.0686

Gnomad NFE exome

AF:

0.0604

Gnomad OTH exome

AF:

0.0654

GnomAD4 exome

AF:

0.0622

AC:

90953

AN:

1461486

Hom.:

3159

Cov.:

AF XY:

0.0617

AC XY:

44842

AN XY:

727032

show subpopulations

African (AFR)

AF:

0.149

AC:

4982

AN:

33470

American (AMR)

AF:

0.0370

AC:

1653

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.0755

AC:

1973

AN:

26116

East Asian (EAS)

AF:

0.0848

AC:

3367

AN:

39694

South Asian (SAS)

AF:

0.0638

AC:

5503

AN:

86202

European-Finnish (FIN)

AF:

0.0708

AC:

3776

AN:

53318

Middle Eastern (MID)

AF:

0.0329

AC:

190

AN:

5768

European-Non Finnish (NFE)

AF:

0.0586

AC:

65164

AN:

1111864

Other (OTH)

AF:

0.0720

AC:

4345

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

5378

10756

16134

21512

26890

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2480

4960

7440

9920

12400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0845

AC:

12846

AN:

152080

Hom.:

654

Cov.:

AF XY:

0.0847

AC XY:

6294

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.147

AC:

6085

AN:

41484

American (AMR)

AF:

0.0457

AC:

699

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0801

AC:

278

AN:

3472

East Asian (EAS)

AF:

0.0719

AC:

368

AN:

5118

South Asian (SAS)

AF:

0.0737

AC:

355

AN:

4820

European-Finnish (FIN)

AF:

0.0701

AC:

742

AN:

10592

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0594

AC:

4036

AN:

67982

Other (OTH)

AF:

0.0701

AC:

148

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

560

1121

1681

2242

2802

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

134

268

402

536

670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0632

Hom.:

313

Bravo

AF:

0.0849

Asia WGS

AF:

0.140

AC:

486

AN:

3478

EpiCase

AF:

0.0576

EpiControl

AF:

0.0541

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.59

PhyloP100

0.39

PromoterAI

0.012

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over