Variant 12-57524385-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_052897.4(MBD6):c.82T>A(p.Cys28Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000882 in 1,599,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000084 ( 0 hom. )

Consequence

MBD6
NM_052897.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.45

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10662919).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBD6	NM_052897.4 linkuse as main transcript	c.82T>A	p.Cys28Ser	missense_variant	3/13	ENST00000355673.8	NP_443129.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBD6	ENST00000355673.8 linkuse as main transcript	c.82T>A	p.Cys28Ser	missense_variant	3/13	1	NM_052897.4	ENSP00000347896	P1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000130

AC:

AN:

237982

Hom.:

AF XY:

0.000132

AC XY:

AN XY:

128764

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000480

Gnomad NFE exome

AF:

0.000277

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000843

AC:

122

AN:

1446918

Hom.:

Cov.:

AF XY:

0.0000946

AC XY:

AN XY:

718850

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000238

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000113

Gnomad4 NFE exome

AF:

0.000101

Gnomad4 OTH exome

AF:

0.0000503

GnomAD4 genome

AF:

0.000125

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000232

Hom.:

Bravo

AF:

0.000140

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000214

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2023

The c.82T>A (p.C28S) alteration is located in exon 3 (coding exon 1) of the MBD6 gene. This alteration results from a T to A substitution at nucleotide position 82, causing the cysteine (C) at amino acid position 28 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.021

T;T;T;T;T;.;.

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.043

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.83

T;.;T;T;T;T;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.11

T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.028

MutationAssessor

Benign

-0.34

.;.;.;N;.;.;.

MutationTaster

Benign

0.77

N;N

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.42

N;N;N;N;N;N;N

REVEL

Uncertain

0.41

Sift

Benign

0.15

T;T;T;D;T;.;T

Sift4G

Benign

0.15

T;T;T;T;T;T;T

Polyphen

0.89

.;.;.;P;.;.;.

Vest4

0.52

MutPred

0.46

Gain of disorder (P = 0.0107);Gain of disorder (P = 0.0107);Gain of disorder (P = 0.0107);Gain of disorder (P = 0.0107);Gain of disorder (P = 0.0107);Gain of disorder (P = 0.0107);.;

MVP

0.21

MPC

0.053

ClinPred

0.10

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over