20-32789189-C-T

Variant names:

• chr20-32789189-C-T
• rs6119285
• NM_006892.4:c.813+177C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency-centromeric instability-facial anomalies syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• facioscapulohumeral muscular dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• immunodeficiency-centromeric instability-facial anomalies syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006892.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNMT3B	NM_006892.4	MANE Select	c.813+177C>T		intron	N/A	NP_008823.1	Q9UBC3-1
	DNMT3B	NM_175850.3		c.849+177C>T		intron	N/A	NP_787046.1	Q9UBC3-6
	DNMT3B	NM_175848.2		c.813+177C>T		intron	N/A	NP_787044.1	Q9UBC3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNMT3B	ENST00000328111.6	TSL:1 MANE Select	c.813+177C>T		intron	N/A	ENSP00000328547.2	Q9UBC3-1
	DNMT3B	ENST00000201963.3	TSL:1	c.849+177C>T		intron	N/A	ENSP00000201963.3	Q9UBC3-6
	DNMT3B	ENST00000348286.6	TSL:1	c.813+177C>T		intron	N/A	ENSP00000337764.2	Q9UBC3-3

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

African (AFR) AF: 0.409 AC: 16960 AN: 41482

American (AMR) AF: 0.0557 AC: 853 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 54 AN: 3470

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5182

South Asian (SAS) AF: 0.0469 AC: 226 AN: 4814

European-Finnish (FIN) AF: 0.0173 AC: 183 AN: 10604

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0226 AC: 1534 AN: 68026

Other (OTH) AF: 0.100 AC: 212 AN: 2112

Alfa AF: 0.164 Hom.: 1839

Bravo AF: 0.147

Asia WGS AF: 0.0670 AC: 235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.033
DANN	Benign	0.36
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6119285; hg19: chr20-31376995;