Variant chr20-32786453-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006892.4(DNMT3B):c.307-49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 1,612,440 control chromosomes in the GnomAD database, including 205,857 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 23099 hom., cov: 34)

Exomes 𝑓: 0.49 ( 182758 hom. )

Consequence

DNMT3B
NM_006892.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.347

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:

DNMT3B (HGNC:):

DNMT3B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 20-32786453-C-T is Benign according to our data. Variant chr20-32786453-C-T is described in ClinVar as [Benign]. Clinvar id is 1170168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNMT3B	NM_006892.4 linkuse as main transcript	c.307-49C>T		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 linkuse as main transcript	c.307-49C>T		intron_variant		1	NM_006892.4	ENSP00000328547.2		Q9UBC3-1

Frequencies

GnomAD3 genomes

AF:

0.534

AC:

81185

AN:

152096

Hom.:

23061

Cov.:

show subpopulations

Gnomad AFR

AF:

0.634

Gnomad AMI

AF:

0.592

Gnomad AMR

AF:

0.569

Gnomad ASJ

AF:

0.500

Gnomad EAS

AF:

0.993

Gnomad SAS

AF:

0.686

Gnomad FIN

AF:

0.451

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.435

Gnomad OTH

AF:

0.488

GnomAD3 exomes

AF:

0.563

AC:

140049

AN:

248646

Hom.:

43224

AF XY:

0.553

AC XY:

74619

AN XY:

134916

show subpopulations

Gnomad AFR exome

AF:

0.639

Gnomad AMR exome

AF:

0.712

Gnomad ASJ exome

AF:

0.495

Gnomad EAS exome

AF:

0.998

Gnomad SAS exome

AF:

0.662

Gnomad FIN exome

AF:

0.456

Gnomad NFE exome

AF:

0.438

Gnomad OTH exome

AF:

0.500

GnomAD4 exome

AF:

0.487

AC:

710423

AN:

1460226

Hom.:

182758

Cov.:

AF XY:

0.489

AC XY:

355196

AN XY:

726446

show subpopulations

Gnomad4 AFR exome

AF:

0.636

Gnomad4 AMR exome

AF:

0.698

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.656

Gnomad4 FIN exome

AF:

0.454

Gnomad4 NFE exome

AF:

0.442

Gnomad4 OTH exome

AF:

0.513

GnomAD4 genome

AF:

0.534

AC:

81281

AN:

152214

Hom.:

23099

Cov.:

AF XY:

0.540

AC XY:

40167

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.634

Gnomad4 AMR

AF:

0.570

Gnomad4 ASJ

AF:

0.500

Gnomad4 EAS

AF:

0.993

Gnomad4 SAS

AF:

0.685

Gnomad4 FIN

AF:

0.451

Gnomad4 NFE

AF:

0.435

Gnomad4 OTH

AF:

0.489

Alfa

AF:

0.484

Hom.:

4022

Bravo

AF:

0.548

Asia WGS

AF:

0.827

AC:

2872

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Centromeric instability of chromosomes 1,9 and 16 and immunodeficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.8

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)

0.010

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