chr1-44213761-C-T

Variant names:

• chr1-44213761-C-T
• rs1643729974
• NM_019100.5:c.8C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BS2

The NM_019100.5(DMAP1):​c.8C>T​(p.Thr3Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000035 in 1,428,130 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: DMAP1 NM_019100.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.77
• Publications: 0 publications found

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]

ENSG00000302536 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMAP1	NM_019100.5	c.8C>T	p.Thr3Met	missense_variant	Exon 1 of 10	ENST00000372289.7	NP_061973.1
DMAP1	NM_001034023.2	c.8C>T	p.Thr3Met	missense_variant	Exon 2 of 11		NP_001029195.1
DMAP1	NM_001034024.2	c.8C>T	p.Thr3Met	missense_variant	Exon 2 of 11		NP_001029196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMAP1	ENST00000372289.7	c.8C>T	p.Thr3Met	missense_variant	Exon 1 of 10	1	NM_019100.5	ENSP00000361363.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000350 AC: 5 AN: 1428130 Hom.: 0 Cov.: 30 AF XY: 0.00000566 AC XY: 4 AN XY: 707328

African (AFR) AF: 0.00 AC: 0 AN: 32448

American (AMR) AF: 0.00 AC: 0 AN: 39980

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25504

East Asian (EAS) AF: 0.00 AC: 0 AN: 37282

South Asian (SAS) AF: 0.00 AC: 0 AN: 81170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51156

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.00000274 AC: 3 AN: 1095676

Other (OTH) AF: 0.0000338 AC: 2 AN: 59180

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.8C>T (p.T3M) alteration is located in exon 1 (coding exon 1) of the DMAP1 gene. This alteration results from a C to T substitution at nucleotide position 8, causing the threonine (T) at amino acid position 3 to be replaced by a methionine (M). 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	Uncertain	0.54
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.13	T;T;T;.;.;T;T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Benign	0.76	D
LIST_S2	Uncertain	0.91	.;D;D;D;D;.;D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.50	T;T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.4	M;.;.;.;.;M;M
PhyloP100		6.8
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.3	N;N;N;N;N;N;N
REVEL	Benign	0.22
Sift	Uncertain	0.0020	D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D
Polyphen		1.0	D;.;.;.;.;D;D
Vest4		0.53
MutPred		0.21		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP		0.49
MPC		2.7
ClinPred		0.99	D
GERP RS		5.1
PromoterAI		-0.057	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.39
gMVP		0.61
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs1643729974; hg19: chr1-44679433;