rs6058894

Positions:

• chr20-32804992-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.2232-346C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0814 in 152,156 control chromosomes in the GnomAD database, including 618 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 0.081 (618 hom., cov: 31)
• Consequence: DNMT3B NM_006892.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNMT3B	NM_006892.4	c.2232-346C>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.2232-346C>T		intron_variant		1	NM_006892.4	ENSP00000328547	A2

Frequencies

GnomAD3 genomes AF: 0.0812 AC: 12347 AN: 152038 Hom.: 612 Cov.: 31

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0441

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.0714

Gnomad SAS AF: 0.0767

Gnomad FIN AF: 0.0700

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0591

Gnomad OTH AF: 0.0684

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

GnomAD4 genome AF: 0.0814 AC: 12380 AN: 152156 Hom.: 618 Cov.: 31 AF XY: 0.0809 AC XY: 6021 AN XY: 74406

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.0439

Gnomad4 ASJ AF: 0.0804

Gnomad4 EAS AF: 0.0716

Gnomad4 SAS AF: 0.0766

Gnomad4 FIN AF: 0.0700

Gnomad4 NFE AF: 0.0591

Gnomad4 OTH AF: 0.0687

Alfa AF: 0.0617 Hom.: 427

Bravo AF: 0.0817

Asia WGS AF: 0.127 AC: 442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.67

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: rs6058894; hg19: chr20-31392798;