Variant 19-1581178-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001281453.2(MBD3):c.591G>A(p.Ser197Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000166 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

MBD3
NM_001281453.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.19

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 19-1581178-C-T is Benign according to our data. Variant chr19-1581178-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 719577.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.19 with no splicing effect.

BS2

High AC in GnomAd4 at 47 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBD3	NM_001281453.2 linkuse as main transcript	c.591G>A	p.Ser197Ser	synonymous_variant	5/7	ENST00000434436.8	NP_001268382.1	O95983-1
MBD3	NM_001281454.2 linkuse as main transcript	c.495G>A	p.Ser165Ser	synonymous_variant	5/7		NP_001268383.1	O95983-2
MBD3	XM_047438939.1 linkuse as main transcript	c.591G>A	p.Ser197Ser	synonymous_variant	5/6		XP_047294895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MBD3	ENST00000434436.8 linkuse as main transcript	c.591G>A	p.Ser197Ser	synonymous_variant	5/7	1	NM_001281453.2	ENSP00000412302.2	O95983-1
ENSG00000267059	ENST00000585937.1 linkuse as main transcript	n.*509G>A		non_coding_transcript_exon_variant	6/7	3		ENSP00000468614.1
ENSG00000267059	ENST00000585937.1 linkuse as main transcript	n.*509G>A		3_prime_UTR_variant	6/7	3		ENSP00000468614.1

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000144

AC:

AN:

250088

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135550

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.0000290

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:

0.000151

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000151

AC:

221

AN:

1461760

Hom.:

Cov.:

AF XY:

0.000143

AC XY:

104

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000138

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.000309

AC:

AN:

152292

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000192

Hom.:

Bravo

AF:

0.000295

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.081

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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