1-44213757-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_019100.5(DMAP1):c.4G>A(p.Ala2Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000558 in 1,578,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

DMAP1
NM_019100.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3253445).

BS2

High AC in GnomAdExome4 at 86 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMAP1	NM_019100.5 link	c.4G>A	p.Ala2Thr	missense_variant	Exon 1 of 10	ENST00000372289.7	NP_061973.1	Q9NPF5
DMAP1	NM_001034023.2 link	c.4G>A	p.Ala2Thr	missense_variant	Exon 2 of 11		NP_001029195.1	Q9NPF5
DMAP1	NM_001034024.2 link	c.4G>A	p.Ala2Thr	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>A	p.Ala2Thr	missense_variant	Exon 1 of 10	1	NM_019100.5	ENSP00000361363.2		Q9NPF5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000103

AC:

AN:

193480

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000240

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000603

AC:

AN:

1425808

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

706002

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32364

American (AMR)

AF:

0.0000253

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:

0.0000124

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:

0.0000749

AC:

AN:

1094408

Other (OTH)

AF:

0.0000338

AC:

AN:

59110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68050

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 28, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.4G>A (p.A2T) alteration is located in exon 1 (coding exon 1) of the DMAP1 gene. This alteration results from a G to A substitution at nucleotide position 4, causing the alanine (A) at amino acid position 2 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

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

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Benign

0.62

LIST_S2

Uncertain

0.91

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

M_CAP

Benign

0.0067

MetaRNN

Benign

0.33

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

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

PhyloP100

5.5

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.99

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

REVEL

Benign

0.076

Sift

Benign

0.14

T;T;T;T;T;T;T

Sift4G

Benign

0.17

T;T;T;T;T;T;T

Polyphen

0.0010

B;.;.;.;.;B;B

Vest4

0.21

MVP

0.36

MPC

1.5

ClinPred

0.75

GERP RS

5.1

PromoterAI

-0.038

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.22

gMVP

0.68

Mutation Taster

=87/13

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

1-44213757-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over