rs16994495

Variant names:

• chr19-1576933-T-C
• rs16994495
• NM_001281453.2:c.*1231A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001281453.2(MBD3):​c.*1231A>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 0.142 in 152,228 control chromosomes in the GnomAD database, including 1,592 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 0.14 (1592 hom., cov: 34)
  • Exomes 𝑓: 0.14 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: MBD3 NM_001281453.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45
• Publications: 6 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]

ENSG00000279009 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBD3	NM_001281453.2	MANE Select	c.*1231A>G		3_prime_UTR	Exon 7 of 7	NP_001268382.1
	MBD3	NM_001281454.2		c.*1231A>G		3_prime_UTR	Exon 7 of 7	NP_001268383.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBD3	ENST00000434436.8	TSL:1 MANE Select	c.*1231A>G		3_prime_UTR	Exon 7 of 7	ENSP00000412302.2
	MBD3	ENST00000156825.5	TSL:1	c.*1231A>G		3_prime_UTR	Exon 7 of 7	ENSP00000156825.2
	MBD3	ENST00000592012.5	TSL:5	n.*1377A>G		non_coding_transcript_exon	Exon 6 of 6	ENSP00000466670.2

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21516 AN: 152110 Hom.: 1586 Cov.: 34

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0997

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0771

Gnomad SAS AF: 0.0874

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.130

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.141 AC: 11 AN: 78 Hom.: 2 Cov.: 0 AF XY: 0.103 AC XY: 6 AN XY: 58

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.300 AC: 3 AN: 10

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.125 AC: 8 AN: 64

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.142 AC: 21547 AN: 152228 Hom.: 1592 Cov.: 34 AF XY: 0.142 AC XY: 10530 AN XY: 74416

African (AFR) AF: 0.134 AC: 5589 AN: 41572

American (AMR) AF: 0.0996 AC: 1524 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 558 AN: 3470

East Asian (EAS) AF: 0.0771 AC: 399 AN: 5176

South Asian (SAS) AF: 0.0869 AC: 420 AN: 4834

European-Finnish (FIN) AF: 0.215 AC: 2273 AN: 10580

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10372 AN: 67976

Other (OTH) AF: 0.131 AC: 276 AN: 2114

Alfa AF: 0.150 Hom.: 196

Bravo AF: 0.134

Asia WGS AF: 0.0880 AC: 307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.43
DANN	Benign	0.14
PhyloP100		-2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16994495; hg19: chr19-1576932;