MBD3 p.Ser197Ser

Variant names:

• chr19-1581177-C-C
• NM_001281453.2:c.

Your query was ambiguous. Multiple possible variants found:

• chr19-1581178--
• chr19-1581178-C-A
• chr19-1581178-C-G
• chr19-1581178-C-T
• chr19-1581178-CGA-ACT
• chr19-1581178-CGA-GCT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001281453.2(MBD3):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MBD3 NM_001281453.2 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.19
• Publications: 0 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]

ENSG00000267059 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBD3	NM_001281453.2	MANE Select	c.		exon_region	Exon 5 of 7	NP_001268382.1	O95983-1
	MBD3	NM_001281454.2		c.		exon_region	Exon 5 of 7	NP_001268383.1	O95983-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBD3	ENST00000434436.8	TSL:1 MANE Select	c.		exon_region	Exon 5 of 7	ENSP00000412302.2	O95983-1
	MBD3	ENST00000156825.5	TSL:1	c.		exon_region	Exon 5 of 7	ENSP00000156825.2	O95983-2
	ENSG00000267059	ENST00000585937.1	TSL:3	n.		exon_region	Exon 6 of 7	ENSP00000468614.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-1581176;