Genetic Variant DMAP1:p.Ser41Phe (chr1-44214366-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019100.5(DMAP1):c.122C>T(p.Ser41Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,820 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. 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. S41Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DMAP1
NM_019100.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.62

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19956434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMAP1	NM_019100.5 link	c.122C>T	p.Ser41Phe	missense_variant	Exon 2 of 10	ENST00000372289.7	NP_061973.1	Q9NPF5
DMAP1	NM_001034023.2 link	c.122C>T	p.Ser41Phe	missense_variant	Exon 3 of 11		NP_001029195.1	Q9NPF5
DMAP1	NM_001034024.2 link	c.122C>T	p.Ser41Phe	missense_variant	Exon 3 of 11		NP_001029196.1	Q9NPF5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMAP1	ENST00000372289.7 link	c.122C>T	p.Ser41Phe	missense_variant	Exon 2 of 10	1	NM_019100.5	ENSP00000361363.2		Q9NPF5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461820

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111992

Other (OTH)

AF:

0.00

AC:

AN:

60390

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

Benign

0.16

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.21

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

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.94

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

M_CAP

Benign

0.011

MetaRNN

Benign

0.20

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

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

PhyloP100

5.6

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.6

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

REVEL

Benign

0.087

Sift

Benign

0.69

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

Sift4G

Benign

0.71

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

Polyphen

0.40

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

Vest4

0.29

MutPred

0.22

Loss of phosphorylation at S41 (P = 0.0057);Loss of phosphorylation at S41 (P = 0.0057);Loss of phosphorylation at S41 (P = 0.0057);Loss of phosphorylation at S41 (P = 0.0057);Loss of phosphorylation at S41 (P = 0.0057);Loss of phosphorylation at S41 (P = 0.0057);Loss of phosphorylation at S41 (P = 0.0057);.;

MVP

0.31

MPC

1.7

ClinPred

0.84

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.42

Mutation Taster

=64/36

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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1-44214366-C-T

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