NM_001281453.2:c.*1239G>C

Variant names:

• chr19-1576925-C-G
• rs12884
• NM_001281453.2:c.*1239G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001281453.2(MBD3):​c.*1239G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,324 control chromosomes in the GnomAD database, including 1,186 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 0.12 (1184 hom., cov: 34)
  • Exomes 𝑓: 0.097 (2 hom.)
• Consequence: MBD3 NM_001281453.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62
• Publications: 5 publications found

Genes affected

MBD3 (HGNC:6918): (methyl-CpG binding domain protein 3) DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. This gene belongs to a family of nuclear proteins which are characterized by the presence of a methyl-CpG binding domain (MBD). The encoded protein is a subunit of the NuRD, a multisubunit complex containing nucleosome remodeling and histone deacetylase activities. Unlike the other family members, the encoded protein is not capable of binding to methylated DNA. The protein mediates the association of metastasis-associated protein 2 with the core histone deacetylase complex. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

ENSG00000279009 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001281453.2. 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
	MBD3	NM_001281453.2	MANE Select	c.*1239G>C		3_prime_UTR	Exon 7 of 7	NP_001268382.1	O95983-1
	MBD3	NM_001281454.2		c.*1239G>C		3_prime_UTR	Exon 7 of 7	NP_001268383.1	O95983-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBD3	ENST00000434436.8	TSL:1 MANE Select	c.*1239G>C		3_prime_UTR	Exon 7 of 7	ENSP00000412302.2	O95983-1
	MBD3	ENST00000156825.5	TSL:1	c.*1239G>C		3_prime_UTR	Exon 7 of 7	ENSP00000156825.2	O95983-2
	MBD3	ENST00000931264.1		c.*1415G>C		3_prime_UTR	Exon 6 of 6	ENSP00000601323.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18314 AN: 152134 Hom.: 1181 Cov.: 34

Gnomad AFR AF: 0.0886

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0850

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0767

Gnomad SAS AF: 0.0788

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.0972 AC: 7 AN: 72 Hom.: 2 Cov.: 0 AF XY: 0.0400 AC XY: 2 AN XY: 50

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.375 AC: 3 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0645 AC: 4 AN: 62

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.120 AC: 18331 AN: 152252 Hom.: 1184 Cov.: 34 AF XY: 0.121 AC XY: 9023 AN XY: 74432

African (AFR) AF: 0.0888 AC: 3691 AN: 41588

American (AMR) AF: 0.0850 AC: 1300 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 474 AN: 3470

East Asian (EAS) AF: 0.0767 AC: 397 AN: 5174

South Asian (SAS) AF: 0.0786 AC: 380 AN: 4832

European-Finnish (FIN) AF: 0.208 AC: 2194 AN: 10572

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9540 AN: 67994

Other (OTH) AF: 0.106 AC: 224 AN: 2114

Alfa AF: 0.0669 Hom.: 74

Bravo AF: 0.112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.96
DANN	Benign	0.45
PhyloP100		-1.6
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: rs12884; hg19: chr19-1576924;