dbSNP rs754556726: MBD3L2:p.Arg129Ser (chr19-7051382-A-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_144614.4(MBD3L2):c.387A>C(p.Arg129Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R129R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000037 ( 0 hom., cov: 21)

Exomes 𝑓: 0.000044 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MBD3L2
NM_144614.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.28

Variant links:

Genes affected

MBD3L2 (HGNC:18532): (methyl-CpG binding domain protein 3 like 2) This gene encodes a protein that is related to methyl-CpG-binding proteins but lacks the methyl-CpG binding domain. The protein has been found in germ cell tumors and some somatic tissues. [provided by RefSeq, Jul 2008]

MBD3L2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06605145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBD3L2	NM_144614.4 link	c.387A>C	p.Arg129Ser	missense_variant	Exon 2 of 2	ENST00000381393.3	NP_653215.2	Q8NHZ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBD3L2	ENST00000381393.3 link	c.387A>C	p.Arg129Ser	missense_variant	Exon 2 of 2	1	NM_144614.4	ENSP00000370800.2		Q8NHZ7

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

135340

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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:

0.0000819

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000211

AC:

AN:

94962

Hom.:

AF XY:

0.0000200

AC XY:

AN XY:

49934

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000119

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000257

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000442

AC:

AN:

520450

Hom.:

Cov.:

AF XY:

0.0000323

AC XY:

AN XY:

278544

show subpopulations

Gnomad4 AFR exome

AF:

0.0000662

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000637

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000271

Gnomad4 NFE exome

AF:

0.0000537

Gnomad4 OTH exome

AF:

0.000104

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000369

AC:

AN:

135340

Hom.:

Cov.:

AF XY:

0.0000306

AC XY:

AN XY:

65300

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000819

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000671

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

1.8

DANN

Benign

0.51

DEOGEN2

Benign

0.047

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00099

LIST_S2

Benign

0.49

M_CAP

Benign

0.00044

MetaRNN

Benign

0.066

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.63

PrimateAI

Benign

0.46

PROVEAN

Benign

0.12

REVEL

Benign

0.24

Sift

Benign

0.77

Sift4G

Benign

0.24

Polyphen

0.89

Vest4

0.095

MutPred

0.26

Loss of methylation at R129 (P = 0.0223);

MVP

0.048

ClinPred

0.077

GERP RS

-1.6

Varity_R

0.12

gMVP

0.14

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over