rs16994495

Positions:

• chr19-1576933-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001281453.2(MBD3):​c.*1231A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,228 control chromosomes in the GnomAD database, including 1,592 homozygotes. 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: 𝑓 0.14 (1592 hom., cov: 34)
  • Exomes 𝑓: 0.14 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: MBD3 NM_001281453.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MBD3	NM_001281453.2	c.*1231A>G		3_prime_UTR_variant	7/7	ENST00000434436.8
MBD3	NM_001281454.2	c.*1231A>G		3_prime_UTR_variant	7/7
MBD3	XM_047438939.1	c.*1407A>G		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MBD3	ENST00000434436.8	c.*1231A>G		3_prime_UTR_variant	7/7	1	NM_001281453.2	P1
	ENST00000624421.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21516 AN: 152110 Hom.: 1586 Cov.: 34

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0997

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0771

Gnomad SAS AF: 0.0874

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.130

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.141 AC: 11 AN: 78 Hom.: 2 Cov.: 0 AF XY: 0.103 AC XY: 6 AN XY: 58

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.125

GnomAD4 genome AF: 0.142 AC: 21547 AN: 152228 Hom.: 1592 Cov.: 34 AF XY: 0.142 AC XY: 10530 AN XY: 74416

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.0996

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.0771

Gnomad4 SAS AF: 0.0869

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.131

Alfa AF: 0.150 Hom.: 196

Bravo AF: 0.134

Asia WGS AF: 0.0880 AC: 307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.43
DANN	Benign	0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs16994495; hg19: chr19-1576932;