rs6058894

Variant names:

• chr20-32804992-C-T
• rs6058894
• NM_006892.4:c.2232-346C>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.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
• Publications: 5 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, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.133 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNMT3B	NM_006892.4	MANE Select	c.2232-346C>T		intron	N/A	NP_008823.1
	DNMT3B	NM_175850.3		c.2208-346C>T		intron	N/A	NP_787046.1
	DNMT3B	NM_175848.2		c.2172-346C>T		intron	N/A	NP_787044.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNMT3B	ENST00000328111.6	TSL:1 MANE Select	c.2232-346C>T		intron	N/A	ENSP00000328547.2
	DNMT3B	ENST00000201963.3	TSL:1	c.2208-346C>T		intron	N/A	ENSP00000201963.3
	DNMT3B	ENST00000348286.6	TSL:1	c.2171+2522C>T		intron	N/A	ENSP00000337764.2

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

African (AFR) AF: 0.136 AC: 5652 AN: 41490

American (AMR) AF: 0.0439 AC: 671 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0804 AC: 279 AN: 3470

East Asian (EAS) AF: 0.0716 AC: 370 AN: 5168

South Asian (SAS) AF: 0.0766 AC: 369 AN: 4820

European-Finnish (FIN) AF: 0.0700 AC: 742 AN: 10598

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0591 AC: 4018 AN: 67994

Other (OTH) AF: 0.0687 AC: 145 AN: 2112

Alfa AF: 0.0638 Hom.: 584

Bravo AF: 0.0817

Asia WGS AF: 0.127 AC: 442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.67
PhyloP100		-0.30
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: rs6058894; hg19: chr20-31392798;