rs6057648

Positions:

• chr20-32797074-C-A
• chr20-32797074-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.1378-113C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 1,604,600 control chromosomes in the GnomAD database, including 836 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 0.042 (259 hom., cov: 33)
  • Exomes 𝑓: 0.022 (577 hom.)
• Consequence: DNMT3B NM_006892.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNMT3B	NM_006892.4	c.1378-113C>A		intron_variant		ENST00000328111.6	NP_008823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNMT3B	ENST00000328111.6	c.1378-113C>A		intron_variant		1	NM_006892.4	ENSP00000328547	A2

Frequencies

GnomAD3 genomes AF: 0.0417 AC: 6344 AN: 152182 Hom.: 257 Cov.: 33

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0455

Gnomad FIN AF: 0.0172

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0195

Gnomad OTH AF: 0.0273

GnomAD3 exomes AF: 0.0251 AC: 6041 AN: 240754 Hom.: 146 AF XY: 0.0248 AC XY: 3258 AN XY: 131488

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.00968

Gnomad ASJ exome AF: 0.00260

Gnomad EAS exome AF: 0.00213

Gnomad SAS exome AF: 0.0438

Gnomad FIN exome AF: 0.0182

Gnomad NFE exome AF: 0.0211

Gnomad OTH exome AF: 0.0157

GnomAD4 exome AF: 0.0224 AC: 32522 AN: 1452300 Hom.: 577 Cov.: 32 AF XY: 0.0224 AC XY: 16183 AN XY: 722758

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.0107

Gnomad4 ASJ exome AF: 0.00264

Gnomad4 EAS exome AF: 0.00101

Gnomad4 SAS exome AF: 0.0402

Gnomad4 FIN exome AF: 0.0168

Gnomad4 NFE exome AF: 0.0204

Gnomad4 OTH exome AF: 0.0233

GnomAD4 genome AF: 0.0418 AC: 6369 AN: 152300 Hom.: 259 Cov.: 33 AF XY: 0.0413 AC XY: 3077 AN XY: 74460

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0167

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.0452

Gnomad4 FIN AF: 0.0172

Gnomad4 NFE AF: 0.0195

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0149 Hom.: 19

Bravo AF: 0.0437

Asia WGS AF: 0.0470 AC: 162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.7
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs6057648; hg19: chr20-31384880;