20-32798008-C-T

Position:

• chr20-32798008-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000328111.6(DNMT3B):​c.1491-452C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 151,806 control chromosomes in the GnomAD database, including 30,337 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.60 (30337 hom., cov: 30)
• Consequence: DNMT3B ENST00000328111.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNMT3B	NM_006892.4	c.1491-452C>T		intron_variant		ENST00000328111.6	NP_008823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNMT3B	ENST00000328111.6	c.1491-452C>T		intron_variant		1	NM_006892.4	ENSP00000328547	A2

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91037 AN: 151688 Hom.: 30282 Cov.: 30

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.550

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.600 AC: 91152 AN: 151806 Hom.: 30337 Cov.: 30 AF XY: 0.605 AC XY: 44868 AN XY: 74162

Gnomad4 AFR AF: 0.857

Gnomad4 AMR AF: 0.601

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.993

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.550

Alfa AF: 0.473 Hom.: 30134

Bravo AF: 0.624

Asia WGS AF: 0.842 AC: 2925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.8
DANN	Benign	0.17

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

Other links and lift over

dbSNP: rs2424921; hg19: chr20-31385814;