19-7051382-A-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144614.4(MBD3L2):​c.387A>T​(p.Arg129Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 21)
• Consequence: MBD3L2 NM_144614.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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

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=0.07529113).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 21

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	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.7
DANN	Benign	0.53
DEOGEN2	Benign	0.047	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00039	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.00044	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.63	N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.076
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		0.13	T
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

Other links and lift over

dbSNP: rs754556726; hg19: chr19-7051393;