NM_001281453.2:c.*1046G>A

Variant names:

• chr19-1577118-C-T
• rs9585
• NM_001281453.2:c.*1046G>A

Variant summary

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

The NM_001281453.2(MBD3):​c.*1046G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 152,486 control chromosomes in the GnomAD database, including 27,258 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 0.56 (27220 hom., cov: 35)
  • Exomes 𝑓: 0.50 (38 hom.)
• Consequence: MBD3 NM_001281453.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 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.*1046G>A		3_prime_UTR	Exon 7 of 7	NP_001268382.1	O95983-1
	MBD3	NM_001281454.2		c.*1046G>A		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.*1046G>A		3_prime_UTR	Exon 7 of 7	ENSP00000412302.2	O95983-1
	MBD3	ENST00000156825.5	TSL:1	c.*1046G>A		3_prime_UTR	Exon 7 of 7	ENSP00000156825.2	O95983-2
	MBD3	ENST00000931264.1		c.*1222G>A		3_prime_UTR	Exon 6 of 6	ENSP00000601323.1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85828 AN: 152122 Hom.: 27184 Cov.: 35

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.533

GnomAD4 exome AF: 0.496 AC: 122 AN: 246 Hom.: 38 Cov.: 0 AF XY: 0.474 AC XY: 92 AN XY: 194

African (AFR) AF: 0.750 AC: 3 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.833 AC: 5 AN: 6

South Asian (SAS) AF: 0.875 AC: 7 AN: 8

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.467 AC: 99 AN: 212

Other (OTH) AF: 0.583 AC: 7 AN: 12

GnomAD4 genome AF: 0.564 AC: 85919 AN: 152240 Hom.: 27220 Cov.: 35 AF XY: 0.569 AC XY: 42374 AN XY: 74420

African (AFR) AF: 0.836 AC: 34754 AN: 41556

American (AMR) AF: 0.586 AC: 8962 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1469 AN: 3472

East Asian (EAS) AF: 0.879 AC: 4540 AN: 5166

South Asian (SAS) AF: 0.674 AC: 3256 AN: 4834

European-Finnish (FIN) AF: 0.409 AC: 4335 AN: 10602

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27063 AN: 68000

Other (OTH) AF: 0.532 AC: 1124 AN: 2112

Alfa AF: 0.492 Hom.: 2586

Bravo AF: 0.588

Asia WGS AF: 0.771 AC: 2678 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.54
PhyloP100		-0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs9585; hg19: chr19-1577117;