NM_015846.4:c.1558G>C

Variant names:

• chr18-50273360-C-G
• rs767264726
• NM_015846.4:c.1558G>C

Variant summary

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

The NM_015846.4(MBD1):​c.1558G>C​(p.Val520Leu) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MBD1 NM_015846.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.732

Genes affected

MBD1 (HGNC:6916): (methyl-CpG binding domain protein 1) The protein encoded by this gene is a member of a family of nuclear proteins related by the presence of a methyl-CpG binding domain (MBD). These proteins are capable of binding specifically to methylated DNA, and some members can also repress transcription from methylated gene promoters. This protein contains multiple domains: MBD at the N-terminus that functions both in binding to methylated DNA and in protein interactions; several CXXC-type zinc finger domains that mediate binding to non-methylated CpG dinucleotides; transcriptional repression domain (TRD) at the C-terminus that is involved in transcription repression and in protein interactions. Numerous alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Feb 2011]

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=0.115478635).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBD1	NM_015846.4	c.1558G>C	p.Val520Leu	missense_variant	Exon 13 of 17	ENST00000269468.10	NP_056671.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBD1	ENST00000269468.10	c.1558G>C	p.Val520Leu	missense_variant	Exon 13 of 17	5	NM_015846.4	ENSP00000269468.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.094	.;T;.;T;T;.;.;.;T;T;.;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.52	D
LIST_S2	Pathogenic	0.97	D;.;D;.;D;D;D;.;D;D;D;.
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.12	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	0.69	.;N;.;N;N;.;N;.;.;.;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.58	.;N;N;.;N;N;.;.;.;.;N;N
REVEL	Benign	0.23
Sift	Benign	0.27	.;T;T;.;T;D;.;.;.;.;T;D
Sift4G	Benign	0.34	T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.11, 0.089, 0.071	.;B;B;B;B;B;.;.;.;.;.;B
Vest4		0.24
MVP		0.48
MPC		0.65
ClinPred		0.074	T
GERP RS		2.9
Varity_R		0.023
gMVP		0.042

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs767264726; hg19: chr18-47799730;