20-32805997-T-C

Position:

• chr20-32805997-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006892.4(DNMT3B):​c.2302-212T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 151,934 control chromosomes in the GnomAD database, including 49,161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.80 (49161 hom., cov: 29)
• Consequence: DNMT3B NM_006892.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.984

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 20-32805997-T-C is Benign according to our data. Variant chr20-32805997-T-C is described in ClinVar as [Benign]. Clinvar id is 1170169.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNMT3B	NM_006892.4	c.2302-212T>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.2302-212T>C		intron_variant		1	NM_006892.4	ENSP00000328547	A2

Frequencies

GnomAD3 genomes AF: 0.796 AC: 120864 AN: 151816 Hom.: 49099 Cov.: 29

Gnomad AFR AF: 0.948

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.779

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

GnomAD4 genome AF: 0.796 AC: 120987 AN: 151934 Hom.: 49161 Cov.: 29 AF XY: 0.801 AC XY: 59425 AN XY: 74224

Gnomad4 AFR AF: 0.949

Gnomad4 AMR AF: 0.786

Gnomad4 ASJ AF: 0.746

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.803

Gnomad4 FIN AF: 0.788

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.779

Alfa AF: 0.728 Hom.: 23433

Bravo AF: 0.804

Asia WGS AF: 0.906 AC: 3148 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Centromeric instability of chromosomes 1,9 and 16 and immunodeficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.77
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: rs4911263; hg19: chr20-31393803;