1-44219807-TG-CT

Variant names:

• chr1-44219807-TG-CT
• NM_019100.5:c.980_981delTGinsCT
• DMAP1 p.Met327Thr

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_019100.5(DMAP1):​c.980_981delTGinsCT​(p.Met327Thr) variant causes a missense, splice region change involving the alteration of a 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DMAP1 NM_019100.5 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.96
• Publications: 0 publications found

Genes affected

DMAP1 (HGNC:18291): (DNA methyltransferase 1 associated protein 1) This gene encodes a subunit of several, distinct complexes involved in the repression or activation of transcription. The encoded protein can independently repress transcription and is targeted to replication foci throughout S phase by interacting directly with the N-terminus of DNA methyltransferase 1. During late S phase, histone deacetylase 2 is added to this complex, providing a means to deacetylate histones in transcriptionally inactive heterochromatin following replication. The encoded protein is also a component of the nucleosome acetyltransferase of H4 complex and interacts with the transcriptional corepressor tumor susceptibility gene 101 and the pro-apoptotic death-associated protein 6, among others. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]

ENSG00000302536 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019100.5. 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
	DMAP1	NM_019100.5	MANE Select	c.980_981delTGinsCT	p.Met327Thr	missense splice_region	N/A	NP_061973.1	Q9NPF5
	DMAP1	NM_001034023.2		c.980_981delTGinsCT	p.Met327Thr	missense splice_region	N/A	NP_001029195.1	Q9NPF5
	DMAP1	NM_001034024.2		c.980_981delTGinsCT	p.Met327Thr	missense splice_region	N/A	NP_001029196.1	Q9NPF5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMAP1	ENST00000372289.7	TSL:1 MANE Select	c.980_981delTGinsCT	p.Met327Thr	missense splice_region	N/A	ENSP00000361363.2	Q9NPF5
	DMAP1	ENST00000315913.9	TSL:1	c.980_981delTGinsCT	p.Met327Thr	missense splice_region	N/A	ENSP00000312697.5	Q9NPF5
	DMAP1	ENST00000361745.10	TSL:1	c.980_981delTGinsCT	p.Met327Thr	missense splice_region	N/A	ENSP00000354697.6	Q9NPF5

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		9.0

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: chr1-44685479;