Variant 12-57524313-G-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.10G>A(p.Gly4Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MBD6
NM_052897.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.75

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:

MBD6 (HGNC:):

MBD6 links:

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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=0.26394215).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBD6	NM_052897.4 linkuse as main transcript	c.10G>A	p.Gly4Ser	missense_variant	3/13	ENST00000355673.8	NP_443129.3	Q96DN6A0A024RBA3Q6P0P0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBD6	ENST00000355673.8 linkuse as main transcript	c.10G>A	p.Gly4Ser	missense_variant	3/13	1	NM_052897.4	ENSP00000347896.3		Q96DN6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000483

AC:

AN:

207200

Hom.:

AF XY:

0.00000896

AC XY:

AN XY:

111584

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:

0.00

Gnomad NFE exome

AF:

0.0000102

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1409522

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

697854

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Oct 08, 2024

The c.10G>A (p.G4S) alteration is located in exon 3 (coding exon 1) of the MBD6 gene. This alteration results from a G to A substitution at nucleotide position 10, causing the glycine (G) at amino acid position 4 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

0.40

BayesDel_addAF

Uncertain

0.056

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

T;T;T;T;T;.

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.76

T;.;T;T;T;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.26

T;T;T;T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.8

.;.;.;L;.;.

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-2.0

N;D;N;N;D;D

REVEL

Benign

0.17

Sift

Benign

0.033

D;D;D;D;D;.

Sift4G

Uncertain

0.038

D;T;T;T;T;T

Polyphen

0.18

.;.;.;B;.;.

Vest4

0.44

MutPred

0.24

Gain of phosphorylation at G4 (P = 0.0298);Gain of phosphorylation at G4 (P = 0.0298);Gain of phosphorylation at G4 (P = 0.0298);Gain of phosphorylation at G4 (P = 0.0298);Gain of phosphorylation at G4 (P = 0.0298);Gain of phosphorylation at G4 (P = 0.0298);

MVP

0.16

MPC

0.046

ClinPred

0.70

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.68

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

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