dbSNP rs144794136: MBD6:p.Arg967Cys (chr12-57528971-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_052897.4(MBD6):c.2899C>T(p.Arg967Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000593 in 1,614,076 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R967H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00062 ( 5 hom. )

Consequence

MBD6
NM_052897.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 3.33

Publications

4 publications found

Variant links:

Genes affected

MBD6 (HGNC:20445): (methyl-CpG binding domain protein 6) Enables chromatin binding activity. Located in chromocenter; fibrillar center; and nucleoplasm. Implicated in autism spectrum disorder. [provided by Alliance of Genome Resources, Apr 2022]

MBD6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015672088).

BP6

Variant 12-57528971-C-T is Benign according to our data. Variant chr12-57528971-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 445772.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052897.4. 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
	MBD6	NM_052897.4	MANE Select	c.2899C>T	p.Arg967Cys	missense	Exon 12 of 13	NP_443129.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MBD6	ENST00000355673.8	TSL:1 MANE Select	c.2899C>T	p.Arg967Cys	missense	Exon 12 of 13	ENSP00000347896.3	Q96DN6
MBD6	ENST00000547545.1	TSL:1	n.1402C>T		non_coding_transcript_exon	Exon 6 of 9	ENSP00000449749.1	A0A0C4DGJ6
MBD6	ENST00000861014.1		c.2899C>T	p.Arg967Cys	missense	Exon 12 of 13	ENSP00000531073.1

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.000959

GnomAD2 exomes

AF:

0.000589

AC:

148

AN:

251398

AF XY:

0.000758

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.000694

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000484

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000621

AC:

908

AN:

1461872

Hom.:

Cov.:

AF XY:

0.000721

AC XY:

524

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33478

American (AMR)

AF:

0.0000447

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000574

AC:

AN:

26136

East Asian (EAS)

AF:

0.000101

AC:

AN:

39692

South Asian (SAS)

AF:

0.00226

AC:

195

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000602

AC:

669

AN:

1112008

Other (OTH)

AF:

0.000331

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

116

173

231

289

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.000322

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41534

American (AMR)

AF:

0.000458

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00187

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000426

AC:

AN:

68022

Other (OTH)

AF:

0.000949

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

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:

0.000497

Hom.:

Bravo

AF:

0.000314

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000568

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000415

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

MBD6-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.049

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0030

MetaRNN

Benign

0.016

MetaSVM

Benign

-0.71

MutationAssessor

Benign

0.34

PhyloP100

3.3

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.83

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.035

Polyphen

1.0

Vest4

0.42

MVP

0.082

MPC

0.34

ClinPred

0.12

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.10

Mutation Taster

=96/4

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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