Genetic Variant DMAP1:p.Ala2Pro (chr1-44213757-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_019100.5(DMAP1):c.4G>C(p.Ala2Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000701 in 1,425,808 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A2T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

DMAP1
NM_019100.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.50

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMAP1	NM_019100.5 link	c.4G>C	p.Ala2Pro	missense_variant	Exon 1 of 10	ENST00000372289.7	NP_061973.1	Q9NPF5
DMAP1	NM_001034023.2 link	c.4G>C	p.Ala2Pro	missense_variant	Exon 2 of 11		NP_001029195.1	Q9NPF5
DMAP1	NM_001034024.2 link	c.4G>C	p.Ala2Pro	missense_variant	Exon 2 of 11		NP_001029196.1	Q9NPF5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMAP1	ENST00000372289.7 link	c.4G>C	p.Ala2Pro	missense_variant	Exon 1 of 10	1	NM_019100.5	ENSP00000361363.2		Q9NPF5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.01e-7

AC:

AN:

1425808

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

706002

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32364

American (AMR)

AF:

0.00

AC:

AN:

39594

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25456

East Asian (EAS)

AF:

0.00

AC:

AN:

37152

South Asian (SAS)

AF:

0.00

AC:

AN:

80966

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51024

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1094408

Other (OTH)

AF:

0.0000169

AC:

AN:

59110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Benign

-0.020

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

T;T;T;.;.;T;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.89

.;D;D;D;D;.;D

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.53

D;D;D;D;D;D;D

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.7

L;.;.;.;.;L;L

PhyloP100

5.5

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-1.6

N;N;N;N;N;N;N

REVEL

Benign

0.091

Sift

Benign

0.042

D;T;T;D;D;D;D

Sift4G

Uncertain

0.022

D;D;D;D;D;D;D

Polyphen

0.74

P;.;.;.;.;P;P

Vest4

0.51

MutPred

0.19

Gain of phosphorylation at T3 (P = 0.1244);Gain of phosphorylation at T3 (P = 0.1244);Gain of phosphorylation at T3 (P = 0.1244);Gain of phosphorylation at T3 (P = 0.1244);Gain of phosphorylation at T3 (P = 0.1244);Gain of phosphorylation at T3 (P = 0.1244);Gain of phosphorylation at T3 (P = 0.1244);

MVP

0.49

MPC

2.3

ClinPred

0.97

GERP RS

5.1

PromoterAI

-0.069

Neutral

(source)

Varity_R

0.66

gMVP

0.81

Mutation Taster

=77/23

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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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1-44213757-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over