rs1053151

Positions:

• chr19-1577209-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBD3	NM_001281453.2	c.*955C>T		3_prime_UTR_variant	7/7	ENST00000434436.8	NP_001268382.1
MBD3	NM_001281454.2	c.*955C>T		3_prime_UTR_variant	7/7		NP_001268383.1
MBD3	XM_047438939.1	c.*1131C>T		3_prime_UTR_variant	6/6		XP_047294895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBD3	ENST00000434436.8	c.*955C>T		3_prime_UTR_variant	7/7	1	NM_001281453.2	ENSP00000412302	P1
MBD3	ENST00000156825.5	c.*955C>T		3_prime_UTR_variant	7/7	1		ENSP00000156825
MBD3	ENST00000590550.6	c.*1131C>T		3_prime_UTR_variant	5/5	2		ENSP00000464718
MBD3	ENST00000592012.5	c.*1101C>T		3_prime_UTR_variant, NMD_transcript_variant	6/6	5		ENSP00000466670

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

Gnomad4 AFR exome AF: 0.750

Gnomad4 ASJ exome AF: 0.500

Gnomad4 SAS exome AF: 1.00

Gnomad4 NFE exome AF: 0.407

Gnomad4 OTH exome AF: 0.500

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

Gnomad4 AFR AF: 0.709

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.583

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.504

Alfa AF: 0.450 Hom.: 4467

Bravo AF: 0.521

Asia WGS AF: 0.564 AC: 1958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.55
DANN	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1053151; hg19: chr19-1577208;