19-1576925-C-G

Position:

• chr19-1576925-C-G

Variant summary

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

The NM_001281453.2(MBD3):​c.*1239G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,324 control chromosomes in the GnomAD database, including 1,186 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 0.12 (1184 hom., cov: 34)
  • Exomes 𝑓: 0.097 (2 hom.)
• Consequence: MBD3 NM_001281453.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MBD3	NM_001281453.2	c.*1239G>C		3_prime_UTR_variant	7/7	ENST00000434436.8
MBD3	NM_001281454.2	c.*1239G>C		3_prime_UTR_variant	7/7
MBD3	XM_047438939.1	c.*1415G>C		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MBD3	ENST00000434436.8	c.*1239G>C		3_prime_UTR_variant	7/7	1	NM_001281453.2	P1
	ENST00000624421.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18314 AN: 152134 Hom.: 1181 Cov.: 34

Gnomad AFR AF: 0.0886

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0850

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0767

Gnomad SAS AF: 0.0788

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.0972 AC: 7 AN: 72 Hom.: 2 Cov.: 0 AF XY: 0.0400 AC XY: 2 AN XY: 50

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.375

Gnomad4 NFE exome AF: 0.0645

GnomAD4 genome AF: 0.120 AC: 18331 AN: 152252 Hom.: 1184 Cov.: 34 AF XY: 0.121 AC XY: 9023 AN XY: 74432

Gnomad4 AFR AF: 0.0888

Gnomad4 AMR AF: 0.0850

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.0767

Gnomad4 SAS AF: 0.0786

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0669 Hom.: 74

Bravo AF: 0.112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.96
DANN	Benign	0.45

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: rs12884; hg19: chr19-1576924;