20-32795547-T-G

Position:

chr20-32795547-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006892.4(DNMT3B):c.1252+13T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 1,613,894 control chromosomes in the GnomAD database, including 156,057 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 15785 hom., cov: 32)

Exomes 𝑓: 0.42 ( 140272 hom. )

Consequence

DNMT3B
NM_006892.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.65

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 20-32795547-T-G is Benign according to our data. Variant chr20-32795547-T-G is described in ClinVar as [Benign]. Clinvar id is 338165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-32795547-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNMT3B	NM_006892.4 link	c.1252+13T>G		intron_variant		ENST00000328111.6	NP_008823.1	Q9UBC3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNMT3B	ENST00000328111.6 link	c.1252+13T>G		intron_variant		1	NM_006892.4	ENSP00000328547.2		Q9UBC3-1

Frequencies

GnomAD3 genomes

AF:

0.440

AC:

66845

AN:

151944

Hom.:

15771

Cov.:

show subpopulations

Gnomad AFR

AF:

0.456

Gnomad AMI

AF:

0.455

Gnomad AMR

AF:

0.518

Gnomad ASJ

AF:

0.417

Gnomad EAS

AF:

0.921

Gnomad SAS

AF:

0.608

Gnomad FIN

AF:

0.382

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.376

Gnomad OTH

AF:

0.407

GnomAD3 exomes

AF:

0.494

AC:

124207

AN:

251356

Hom.:

34571

AF XY:

0.487

AC XY:

66179

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.457

Gnomad AMR exome

AF:

0.676

Gnomad ASJ exome

AF:

0.419

Gnomad EAS exome

AF:

0.925

Gnomad SAS exome

AF:

0.595

Gnomad FIN exome

AF:

0.388

Gnomad NFE exome

AF:

0.378

Gnomad OTH exome

AF:

0.434

GnomAD4 exome

AF:

0.423

AC:

618817

AN:

1461832

Hom.:

140272

Cov.:

AF XY:

0.426

AC XY:

310143

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.453

Gnomad4 AMR exome

AF:

0.659

Gnomad4 ASJ exome

AF:

0.422

Gnomad4 EAS exome

AF:

0.914

Gnomad4 SAS exome

AF:

0.591

Gnomad4 FIN exome

AF:

0.384

Gnomad4 NFE exome

AF:

0.384

Gnomad4 OTH exome

AF:

0.437

GnomAD4 genome

AF:

0.440

AC:

66892

AN:

152062

Hom.:

15785

Cov.:

AF XY:

0.447

AC XY:

33233

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.456

Gnomad4 AMR

AF:

0.519

Gnomad4 ASJ

AF:

0.417

Gnomad4 EAS

AF:

0.921

Gnomad4 SAS

AF:

0.608

Gnomad4 FIN

AF:

0.382

Gnomad4 NFE

AF:

0.376

Gnomad4 OTH

AF:

0.408

Alfa

AF:

0.378

Hom.:

11431

Bravo

AF:

0.452

Asia WGS

AF:

0.690

AC:

2396

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 09, 2018	This variant is associated with the following publications: (PMID: 26851945) -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Immunodeficiency-centromeric instability-facial anomalies syndrome 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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 -

Centromeric instability of chromosomes 1,9 and 16 and immunodeficiency

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

-0.91

CADD

Benign

0.35

DANN

Benign

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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