Genetic Variant MBD3:p.Lys92Lys (chr19-1584672-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001281453.2(MBD3):c.276G>A(p.Lys92Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,611,746 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00089 ( 9 hom. )

Consequence

MBD3
NM_001281453.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.522

Publications

1 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:

ENSG00000267059 (HGNC:):

ENSG00000267059 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 19-1584672-C-T is Benign according to our data. Variant chr19-1584672-C-T is described in ClinVar as Benign. ClinVar VariationId is 712135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.522 with no splicing effect.

BS2

High AC in GnomAd4 at 653 AD gene.

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.276G>A	p.Lys92Lys	synonymous	Exon 3 of 7	NP_001268382.1	O95983-1
	MBD3	NM_001281454.2		c.180G>A	p.Lys60Lys	synonymous	Exon 3 of 7	NP_001268383.1	O95983-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MBD3	ENST00000434436.8	TSL:1 MANE Select	c.276G>A	p.Lys92Lys	synonymous	Exon 3 of 7	ENSP00000412302.2	O95983-1
MBD3	ENST00000156825.5	TSL:1	c.180G>A	p.Lys60Lys	synonymous	Exon 3 of 7	ENSP00000156825.2	O95983-2
ENSG00000267059	ENST00000585937.1	TSL:3	n.*194G>A		non_coding_transcript_exon	Exon 4 of 7	ENSP00000468614.1

Frequencies

GnomAD3 genomes

AF:

0.00429

AC:

653

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0132

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00185

AC:

458

AN:

247292

AF XY:

0.00163

show subpopulations

Gnomad AFR exome

AF:

0.0131

Gnomad AMR exome

AF:

0.00368

Gnomad ASJ exome

AF:

0.00350

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000600

Gnomad OTH exome

AF:

0.00246

GnomAD4 exome

AF:

0.000892

AC:

1302

AN:

1459434

Hom.:

Cov.:

AF XY:

0.000897

AC XY:

651

AN XY:

726134

show subpopulations

African (AFR)

AF:

0.0140

AC:

469

AN:

33456

American (AMR)

AF:

0.00418

AC:

187

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00387

AC:

101

AN:

26100

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51474

Middle Eastern (MID)

AF:

0.00590

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000331

AC:

368

AN:

1111680

Other (OTH)

AF:

0.00229

AC:

138

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

152

228

304

380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<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:

0.00429

AC:

653

AN:

152312

Hom.:

Cov.:

AF XY:

0.00400

AC XY:

298

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0132

AC:

547

AN:

41574

American (AMR)

AF:

0.00372

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000397

AC:

AN:

68018

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

103

138

172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00284

Hom.:

Bravo

AF:

0.00496

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00131

EpiControl

AF:

0.000889

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

8.4

(source)

DANN

Benign

0.69

PhyloP100

0.52

Mutation Taster

=98/2

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over