NM_006892.4:c.-105C>G

Variant names:

• chr20-32762601-C-G
• rs767131541
• NM_006892.4:c.-105C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006892.4(DNMT3B):​c.-105C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNMT3B NM_006892.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.590
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.04).

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.-105C>G		5_prime_UTR	Exon 1 of 23	NP_008823.1	Q9UBC3-1
	DNMT3B	NM_175848.2		c.-105C>G		5_prime_UTR	Exon 1 of 22	NP_787044.1	Q9UBC3-2
	DNMT3B	NM_001424351.1		c.-105C>G		5_prime_UTR	Exon 1 of 22	NP_001411280.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNMT3B	ENST00000328111.6	TSL:1 MANE Select	c.-105C>G		5_prime_UTR	Exon 1 of 23	ENSP00000328547.2	Q9UBC3-1
	DNMT3B	ENST00000348286.6	TSL:1	c.-105C>G		5_prime_UTR	Exon 1 of 20	ENSP00000337764.2	Q9UBC3-3
	DNMT3B	ENST00000353855.6	TSL:5	c.-105C>G		5_prime_UTR	Exon 1 of 22	ENSP00000313397.4	Q9UBC3-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 174634 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 107182

African (AFR) AF: 0.00 AC: 0 AN: 3668

American (AMR) AF: 0.00 AC: 0 AN: 16840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7158

East Asian (EAS) AF: 0.00 AC: 0 AN: 1490

South Asian (SAS) AF: 0.00 AC: 0 AN: 39506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 818

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 89650

Other (OTH) AF: 0.00 AC: 0 AN: 7224

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	19
DANN	Benign	0.94
PhyloP100		-0.59
PromoterAI		-0.10	Neutral

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: rs767131541; hg19: chr20-31350407;