rs1053151

Variant names:

• chr19-1577209-G-A
• rs1053151
• NM_001281453.2:c.*955C>T

Variant summary

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

The NM_001281453.2(MBD3):​c.*955C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 152,342 control chromosomes in the GnomAD database, including 20,422 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 0.50 (20408 hom., cov: 35)
  • Exomes 𝑓: 0.45 (14 hom.)
• Consequence: MBD3 NM_001281453.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 12 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBD3	NM_001281453.2	MANE Select	c.*955C>T		3_prime_UTR	Exon 7 of 7	NP_001268382.1
	MBD3	NM_001281454.2		c.*955C>T		3_prime_UTR	Exon 7 of 7	NP_001268383.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBD3	ENST00000434436.8	TSL:1 MANE Select	c.*955C>T		3_prime_UTR	Exon 7 of 7	ENSP00000412302.2
	MBD3	ENST00000156825.5	TSL:1	c.*955C>T		3_prime_UTR	Exon 7 of 7	ENSP00000156825.2
	MBD3	ENST00000592012.5	TSL:5	n.*1101C>T		non_coding_transcript_exon	Exon 6 of 6	ENSP00000466670.2

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75587 AN: 152094 Hom.: 20366 Cov.: 35

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.507

GnomAD4 exome AF: 0.454 AC: 59 AN: 130 Hom.: 14 Cov.: 0 AF XY: 0.435 AC XY: 40 AN XY: 92

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) AC: 0 AN: 0

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

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

Middle Eastern (MID) AF: 0.833 AC: 5 AN: 6

European-Non Finnish (NFE) AF: 0.407 AC: 44 AN: 108

Other (OTH) AF: 0.500 AC: 4 AN: 8

GnomAD4 genome AF: 0.497 AC: 75683 AN: 152212 Hom.: 20408 Cov.: 35 AF XY: 0.494 AC XY: 36736 AN XY: 74416

African (AFR) AF: 0.709 AC: 29474 AN: 41544

American (AMR) AF: 0.515 AC: 7875 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1504 AN: 3472

East Asian (EAS) AF: 0.493 AC: 2552 AN: 5174

South Asian (SAS) AF: 0.583 AC: 2812 AN: 4826

European-Finnish (FIN) AF: 0.304 AC: 3229 AN: 10608

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26657 AN: 67980

Other (OTH) AF: 0.504 AC: 1064 AN: 2110

Alfa AF: 0.462 Hom.: 5238

Bravo AF: 0.521

Asia WGS AF: 0.564 AC: 1958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.55
DANN	Benign	0.85
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs1053151; hg19: chr19-1577208;