Genetic Variant MBD3:c.*1046G>A (chr19-1577118-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001281453.2(MBD3):c.*1046G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 152,486 control chromosomes in the GnomAD database, including 27,258 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 0.56 ( 27220 hom., cov: 35)

Exomes 𝑓: 0.50 ( 38 hom. )

Consequence

MBD3
NM_001281453.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.259

Publications

8 publications found

Variant links:

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]

MBD3 links:

ENSG00000279009 (HGNC:):

ENSG00000279009 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MBD3	NM_001281453.2 link	c.*1046G>A	3_prime_UTR_variant	Exon 7 of 7	ENST00000434436.8	NP_001268382.1	O95983-1
MBD3	NM_001281454.2 link	c.*1046G>A	3_prime_UTR_variant	Exon 7 of 7		NP_001268383.1	O95983-2
MBD3	XM_047438939.1 link	c.*1222G>A	3_prime_UTR_variant	Exon 6 of 6		XP_047294895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBD3	ENST00000434436.8 link	c.*1046G>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_001281453.2	ENSP00000412302.2		O95983-1

Frequencies

GnomAD3 genomes

AF:

0.564

AC:

85828

AN:

152122

Hom.:

27184

Cov.:

show subpopulations

Gnomad AFR

AF:

0.836

Gnomad AMI

AF:

0.314

Gnomad AMR

AF:

0.586

Gnomad ASJ

AF:

0.423

Gnomad EAS

AF:

0.879

Gnomad SAS

AF:

0.676

Gnomad FIN

AF:

0.409

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.398

Gnomad OTH

AF:

0.533

GnomAD4 exome

AF:

0.496

AC:

122

AN:

246

Hom.:

Cov.:

AF XY:

0.474

AC XY:

AN XY:

194

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.833

AC:

AN:

South Asian (SAS)

AF:

0.875

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.467

AC:

AN:

212

Other (OTH)

AF:

0.583

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.564

AC:

85919

AN:

152240

Hom.:

27220

Cov.:

AF XY:

0.569

AC XY:

42374

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.836

AC:

34754

AN:

41556

American (AMR)

AF:

0.586

AC:

8962

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.423

AC:

1469

AN:

3472

East Asian (EAS)

AF:

0.879

AC:

4540

AN:

5166

South Asian (SAS)

AF:

0.674

AC:

3256

AN:

4834

European-Finnish (FIN)

AF:

0.409

AC:

4335

AN:

10602

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.398

AC:

27063

AN:

68000

Other (OTH)

AF:

0.532

AC:

1124

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1741

3482

5223

6964

8705

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

708

1416

2124

2832

3540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.492

Hom.:

2586

Bravo

AF:

0.588

Asia WGS

AF:

0.771

AC:

2678

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.6

(source)

DANN

Benign

0.54

PhyloP100

-0.26

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over