dbSNP rs2238588: MBD3:c.*1235A>G (chr19-1576929-T-C) – 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.*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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.89

Publications

5 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:

Genome browser will be placed here

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MBD3	NM_001281453.2 link	c.*1235A>G	3_prime_UTR_variant	Exon 7 of 7	ENST00000434436.8	NP_001268382.1	O95983-1
MBD3	NM_001281454.2 link	c.*1235A>G	3_prime_UTR_variant	Exon 7 of 7		NP_001268383.1	O95983-2
MBD3	XM_047438939.1 link	c.*1411A>G	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.*1235A>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_001281453.2	ENSP00000412302.2		O95983-1

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19629

AN:

152126

Hom.:

1367

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.0862

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.300

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0968

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.129

AC:

19644

AN:

152244

Hom.:

1369

Cov.:

AF XY:

0.129

AC XY:

9637

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0933

AC:

3878

AN:

41582

American (AMR)

AF:

0.0918

AC:

1405

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

546

AN:

3468

East Asian (EAS)

AF:

0.0775

AC:

401

AN:

5174

South Asian (SAS)

AF:

0.0870

AC:

420

AN:

4830

European-Finnish (FIN)

AF:

0.215

AC:

2271

AN:

10584

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.152

AC:

10333

AN:

67986

Other (OTH)

AF:

0.121

AC:

256

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

947

1894

2841

3788

4735

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

220

440

660

880

1100

<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:

0.143

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

(source)

DANN

Benign

0.21

PhyloP100

-1.9

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over