rs2238588

Positions:

• chr19-1576929-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001281453.2(MBD3):​c.*1235A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,244 control chromosomes in the GnomAD database, including 1,369 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 0.13 (1369 hom., cov: 34)
  • Exomes 𝑓: 0.13 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: MBD3 NM_001281453.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

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]

(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 (NFE) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MBD3	NM_001281453.2	c.*1235A>G		3_prime_UTR_variant	7/7	ENST00000434436.8
MBD3	NM_001281454.2	c.*1235A>G		3_prime_UTR_variant	7/7
MBD3	XM_047438939.1	c.*1411A>G		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MBD3	ENST00000434436.8	c.*1235A>G		3_prime_UTR_variant	7/7	1	NM_001281453.2	P1
	ENST00000624421.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19629 AN: 152126 Hom.: 1367 Cov.: 34

Gnomad AFR AF: 0.0931

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0919

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.0775

Gnomad SAS AF: 0.0873

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.120

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.128 AC: 10 AN: 78 Hom.: 2 Cov.: 0 AF XY: 0.0862 AC XY: 5 AN XY: 58

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.0968

GnomAD4 genome AF: 0.129 AC: 19644 AN: 152244 Hom.: 1369 Cov.: 34 AF XY: 0.129 AC XY: 9637 AN XY: 74428

Gnomad4 AFR AF: 0.0933

Gnomad4 AMR AF: 0.0918

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.0775

Gnomad4 SAS AF: 0.0870

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.121

Alfa AF: 0.143 Hom.: 174

Bravo AF: 0.120

Asia WGS AF: 0.0800 AC: 279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.1
DANN	Benign	0.21

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: rs2238588; hg19: chr19-1576928;