NM_144614.4:c.387A>C

Variant names:

• chr19-7051382-A-C
• rs754556726
• NM_144614.4:c.387A>C

Variant summary

Our verdict is Likely benign. The variant received -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. 16/21 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06605145).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144614.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBD3L2	NM_144614.4	MANE Select	c.387A>C	p.Arg129Ser	missense	Exon 2 of 2	NP_653215.2	Q8NHZ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBD3L2	ENST00000381393.3	TSL:1 MANE Select	c.387A>C	p.Arg129Ser	missense	Exon 2 of 2	ENSP00000370800.2	Q8NHZ7

Frequencies

GnomAD3 genomes AF: 0.0000369 AC: 5 AN: 135340 Hom.: 0 Cov.: 21

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

GnomAD2 exomes AF: 0.0000211 AC: 2 AN: 94962 AF XY: 0.0000200

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 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: 23 AN: 520450 Hom.: 0 Cov.: 0 AF XY: 0.0000323 AC XY: 9 AN XY: 278544

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000662 AC: 1 AN: 15102

American (AMR) AF: 0.00 AC: 0 AN: 32412

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18288

East Asian (EAS) AF: 0.0000637 AC: 2 AN: 31384

South Asian (SAS) AF: 0.00 AC: 0 AN: 57006

European-Finnish (FIN) AF: 0.0000271 AC: 1 AN: 36902

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2300

European-Non Finnish (NFE) AF: 0.0000537 AC: 16 AN: 298148

Other (OTH) AF: 0.000104 AC: 3 AN: 28908

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000369 AC: 5 AN: 135340 Hom.: 0 Cov.: 21 AF XY: 0.0000306 AC XY: 2 AN XY: 65300

African (AFR) AF: 0.00 AC: 0 AN: 37374

American (AMR) AF: 0.00 AC: 0 AN: 13074

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3194

East Asian (EAS) AF: 0.00 AC: 0 AN: 4576

South Asian (SAS) AF: 0.00 AC: 0 AN: 3696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 296

European-Non Finnish (NFE) AF: 0.0000819 AC: 5 AN: 61060

Other (OTH) AF: 0.00 AC: 0 AN: 1790

Alfa AF: 0.00 Hom.: 7

ExAC AF: 0.0000671 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.8
DANN	Benign	0.51
DEOGEN2	Benign	0.047	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00099	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.00044	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.63	N
PhyloP100		-1.3
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.24
Sift	Benign	0.77	T
Sift4G	Benign	0.24	T
Polyphen		0.89	P
Vest4		0.095
MutPred		0.26		Loss of methylation at R129 (P = 0.0223)
MVP		0.048
ClinPred		0.077	T
GERP RS		-1.6
Varity_R		0.12
gMVP		0.14
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs754556726; hg19: chr19-7051393;