chr19-1577118-C-T

Position:

• chr19-1577118-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBD3	NM_001281453.2	c.*1046G>A		3_prime_UTR_variant	7/7	ENST00000434436.8	NP_001268382.1
MBD3	NM_001281454.2	c.*1046G>A		3_prime_UTR_variant	7/7		NP_001268383.1
MBD3	XM_047438939.1	c.*1222G>A		3_prime_UTR_variant	6/6		XP_047294895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBD3	ENST00000434436	c.*1046G>A		3_prime_UTR_variant	7/7	1	NM_001281453.2	ENSP00000412302.2

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

Gnomad4 AFR exome AF: 0.750

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.833

Gnomad4 SAS exome AF: 0.875

Gnomad4 NFE exome AF: 0.467

Gnomad4 OTH exome AF: 0.583

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

Gnomad4 AFR AF: 0.836

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.879

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.409

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.532

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9585; hg19: chr19-1577117;