Genetic Variant MBD3:c.*955C>T (chr19-1577209-G-A) – 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.*955C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 152,342 control chromosomes in the GnomAD database, including 20,422 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 0.50 ( 20408 hom., cov: 35)

Exomes 𝑓: 0.45 ( 14 hom. )

Consequence

MBD3
NM_001281453.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.03

Publications

12 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MBD3	NM_001281453.2 link	c.*955C>T	3_prime_UTR_variant	Exon 7 of 7	ENST00000434436.8	NP_001268382.1	O95983-1
MBD3	NM_001281454.2 link	c.*955C>T	3_prime_UTR_variant	Exon 7 of 7		NP_001268383.1	O95983-2
MBD3	XM_047438939.1 link	c.*1131C>T	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.*955C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_001281453.2	ENSP00000412302.2		O95983-1

Frequencies

GnomAD3 genomes

AF:

0.497

AC:

75587

AN:

152094

Hom.:

20366

Cov.:

show subpopulations

Gnomad AFR

AF:

0.709

Gnomad AMI

AF:

0.382

Gnomad AMR

AF:

0.515

Gnomad ASJ

AF:

0.433

Gnomad EAS

AF:

0.494

Gnomad SAS

AF:

0.583

Gnomad FIN

AF:

0.304

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.392

Gnomad OTH

AF:

0.507

GnomAD4 exome

AF:

0.454

AC:

AN:

130

Hom.:

Cov.:

AF XY:

0.435

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.833

AC:

AN:

European-Non Finnish (NFE)

AF:

0.407

AC:

AN:

108

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.497

AC:

75683

AN:

152212

Hom.:

20408

Cov.:

AF XY:

0.494

AC XY:

36736

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.709

AC:

29474

AN:

41544

American (AMR)

AF:

0.515

AC:

7875

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.433

AC:

1504

AN:

3472

East Asian (EAS)

AF:

0.493

AC:

2552

AN:

5174

South Asian (SAS)

AF:

0.583

AC:

2812

AN:

4826

European-Finnish (FIN)

AF:

0.304

AC:

3229

AN:

10608

Middle Eastern (MID)

AF:

0.578

AC:

170

AN:

294

European-Non Finnish (NFE)

AF:

0.392

AC:

26657

AN:

67980

Other (OTH)

AF:

0.504

AC:

1064

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1905

3809

5714

7618

9523

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.462

Hom.:

5238

Bravo

AF:

0.521

Asia WGS

AF:

0.564

AC:

1958

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.55

(source)

DANN

Benign

0.85

PhyloP100

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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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chr19-1577209-G-A

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