20-32777913-T-C

Position:

• chr20-32777913-T-C

Variant summary

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

The NM_006892.4(DNMT3B):​c.-6-2405T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,060 control chromosomes in the GnomAD database, including 29,920 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 (29920 hom., cov: 32)
• Consequence: DNMT3B NM_006892.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

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=-0.92).
• 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	c.-6-2405T>C		intron_variant		ENST00000328111.6	NP_008823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNMT3B	ENST00000328111.6	c.-6-2405T>C		intron_variant		1	NM_006892.4	ENSP00000328547	A2

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90632 AN: 151942 Hom.: 29870 Cov.: 32

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.597 AC: 90740 AN: 152060 Hom.: 29920 Cov.: 32 AF XY: 0.601 AC XY: 44704 AN XY: 74328

Gnomad4 AFR AF: 0.843

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.993

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.548

Alfa AF: 0.479 Hom.: 25008

Bravo AF: 0.620

Asia WGS AF: 0.841 AC: 2921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.62
DANN	Benign	0.32

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: rs6058883; hg19: chr20-31365719;