Genetic Variant DMAP1:p.Met327Thr (chr1-44219807-T-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000372289.7(DMAP1):c.980T>C(p.Met327Thr) 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. 3/3 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
ENST00000372289.7 missense, splice_region

Scores

Splicing: ADA: 0.3413

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.17

Publications

0 publications found

Variant links:

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]

DMAP1 links:

ENSG00000302536 (HGNC:):

ENSG00000302536 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.849

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000372289.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DMAP1	NM_019100.5	MANE Select	c.980T>C	p.Met327Thr	missense splice_region	Exon 8 of 10	NP_061973.1
DMAP1	NM_001034023.2		c.980T>C	p.Met327Thr	missense splice_region	Exon 9 of 11	NP_001029195.1
DMAP1	NM_001034024.2		c.980T>C	p.Met327Thr	missense splice_region	Exon 9 of 11	NP_001029196.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DMAP1	ENST00000372289.7	TSL:1 MANE Select	c.980T>C	p.Met327Thr	missense splice_region	Exon 8 of 10	ENSP00000361363.2
DMAP1	ENST00000315913.9	TSL:1	c.980T>C	p.Met327Thr	missense splice_region	Exon 9 of 11	ENSP00000312697.5
DMAP1	ENST00000361745.10	TSL:1	c.980T>C	p.Met327Thr	missense splice_region	Exon 9 of 11	ENSP00000354697.6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Pathogenic

0.42

BayesDel_noAF

Pathogenic

0.36

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.45

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.018

MetaRNN

Pathogenic

0.85

MetaSVM

Benign

-0.64

MutationAssessor

Uncertain

2.3

PhyloP100

7.2

PrimateAI

Pathogenic

0.91

PROVEAN

Pathogenic

-4.5

REVEL

Uncertain

0.43

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Polyphen

0.77

Vest4

0.88

MutPred

0.70

Gain of methylation at K328 (P = 0.0245)

MVP

0.47

MPC

0.99

ClinPred

0.99

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.73

gMVP

0.83

Mutation Taster

=3/97

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.34

dbscSNV1_RF

Benign

0.68

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over