18-50273807-TGG-CGT

Variant names:

• chr18-50273807-TGG-CGT
• NM_015846.4:c.1201_1203delCCAinsACG
• MBD1 p.Pro401Thr

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_015846.4(MBD1):​c.1201_1203delCCAinsACG​(p.Pro401Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P401A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MBD1 NM_015846.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015846.4. 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
	MBD1	NM_015846.4	MANE Select	c.1201_1203delCCAinsACG	p.Pro401Thr	missense	N/A	NP_056671.2
	MBD1	NM_001323942.2		c.1276_1278delCCAinsACG	p.Pro426Thr	missense	N/A	NP_001310871.1	A0A994J7H0
	MBD1	NM_001323947.2		c.1276_1278delCCAinsACG	p.Pro426Thr	missense	N/A	NP_001310876.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBD1	ENST00000269468.10	TSL:5 MANE Select	c.1201_1203delCCAinsACG	p.Pro401Thr	missense	N/A	ENSP00000269468.5	Q9UIS9-1
	MBD1	ENST00000590208.5	TSL:1	c.1201_1203delCCAinsACG	p.Pro401Thr	missense	N/A	ENSP00000468785.1	Q9UIS9-12
	MBD1	ENST00000588937.5	TSL:1	c.1132_1134delCCAinsACG	p.Pro378Thr	missense	N/A	ENSP00000467763.1	Q9UIS9-2

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr18-47800177;