rs12760076

chr1-44219807-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_019100.5(DMAP1):c.980T>A(p.Met327Lys) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. 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
• Scores: Splicing: ADA: 0.3413
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.17

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.89

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMAP1	NM_019100.5	c.980T>A	p.Met327Lys	missense_variant, splice_region_variant	8/10	ENST00000372289.7
DMAP1	NM_001034023.2	c.980T>A	p.Met327Lys	missense_variant, splice_region_variant	9/11
DMAP1	NM_001034024.2	c.980T>A	p.Met327Lys	missense_variant, splice_region_variant	9/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMAP1	ENST00000372289.7	c.980T>A	p.Met327Lys	missense_variant, splice_region_variant	8/10	1	NM_019100.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.39
Cadd	Pathogenic	34
Dann	Uncertain	0.98
DEOGEN2	Uncertain	0.64	D;D;D
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.031	D
MetaRNN	Pathogenic	0.89	D;D;D
MetaSVM	Benign	-0.32	T
MutationAssessor	Uncertain	2.3	M;M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-4.6	D;D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		0.96	D;D;D
Vest4		0.93
MutPred		0.72		Gain of solvent accessibility (P = 0.0038);Gain of solvent accessibility (P = 0.0038);Gain of solvent accessibility (P = 0.0038);
MVP		0.48
MPC		1.5
ClinPred		0.99	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.89
gMVP		0.94

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.34
dbscSNV1_RF	Benign	0.66
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.27		Position offset: -27

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

Publications

LitVar

Other links and lift over

dbSNP: rs12760076; hg19: chr1-44685479;