20-32789189-C-T

Position:

• chr20-32789189-C-T

Variant summary

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

The NM_006892.4(DNMT3B):​c.813+177C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,200 control chromosomes in the GnomAD database, including 3,553 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 0.13 (3553 hom., cov: 33)
• Consequence: DNMT3B NM_006892.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNMT3B	NM_006892.4	c.813+177C>T		intron_variant		ENST00000328111.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNMT3B	ENST00000328111.6	c.813+177C>T		intron_variant		1	NM_006892.4	A2

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20045 AN: 152082 Hom.: 3544 Cov.: 33

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.0559

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0482

Gnomad FIN AF: 0.0173

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0225

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.132 AC: 20088 AN: 152200 Hom.: 3553 Cov.: 33 AF XY: 0.129 AC XY: 9614 AN XY: 74414

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.0557

Gnomad4 ASJ AF: 0.0156

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.0469

Gnomad4 FIN AF: 0.0173

Gnomad4 NFE AF: 0.0226

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0573 Hom.: 214

Bravo AF: 0.147

Asia WGS AF: 0.0670 AC: 235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.033
DANN	Benign	0.36

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: rs6119285; hg19: chr20-31376995;